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Sample records for decreased candicidal activity

  1. Altered polymorphonuclear leukocyte Fc gamma R expression contributes to decreased candicidal activity during intraabdominal sepsis

    International Nuclear Information System (INIS)

    Simms, H.H.; D'Amico, R.; Monfils, P.; Burchard, K.W.

    1991-01-01

    We investigated the effects of untreated intraabdominal sepsis on polymorphonuclear leukocyte (PMN) candicidal activity. Two groups of swine were studied. Group I (n=6) underwent sham laparotomy, group II (n=7) underwent cecal ligation and incision. Untreated intraabdominal sepsis resulted in a progressive decrease in PMN candicidal activity. Concomitant rosetting and phagocytosis assays demonstrated a decrease in both the attachment and phagocytosis of Candida albicans opsonized with both normal and septic swine serum by PMNs in group II. Iodine 125-labeled swine immunoglobulin G (IgG) and fluorescein isothioalanate (FITC)-labeled swine IgG were used to investigate Fc gamma receptor ligand interactions. Scatchard analyses demonstrated a progressive decline in both the binding affinity constant and number of IgG molecules bound per PMN. Stimulation of the oxidative burst markedly reduced 125I-labeled IgG binding in both group I and group II, with a greater decrement being seen in animals with intraabdominal sepsis. Further, in group II, PMN recycling of the Fc gamma receptor to the cell surface after generation of the oxidative burst was reduced by postoperative day 4. Binding of monoclonal antibodies to Fc gamma receptor II, but not Fc gamma receptor I/III markedly reduced intracellular candicidal activity. Immunofluorescence studies revealed a homogeneous pattern of FITC-IgG uptake by nearly all group I PMNs, whereas by postoperative day 8 a substantial number of PMNs from group II failed to internalize the FITC-IgG. These studies suggest that untreated intraabdominal sepsis reduces PMN candicidal activity and that this is due, in part, to altered PMN Fc gamma receptor ligand interactions

  2. Decreased active vasodilator sensitivity in aged skin.

    Science.gov (United States)

    Kenney, W L; Morgan, A L; Farquhar, W B; Brooks, E M; Pierzga, J M; Derr, J A

    1997-04-01

    Older men and women respond to local and reflex-mediated heat stress with an attenuated increase in cutaneous vascular conductance (CVC). This study was performed to test the hypothesis that an augmented or sustained noradrenergic vasoconstriction (VC) may play a role in this age-related difference. Fifteen young (22 +/- 1 yr) and 15 older (66 +/- 1 yr) men exercised at 50% peak oxygen uptake in a 36 degrees C environment. Skin perfusion was monitored at two sites on the right forearm by laser-Doppler flowmetry: one site pretreated with bretylium tosylate (BT) to block the local release of norepinephrine and thus VC and an adjacent control site. Blockade of reflex VC was verified during whole body cooling using a water-perfused suit. CVC (perfusion divided by mean arterial pressure) at each site was reported as a percentage of the maximal CVC (%CVCmax) induced at the end of each experiment by prolonged local heating at 42 degrees C. Neither age nor BT affected the %CVCmax (75-86%) attained at high core temperatures. During the early rise phase of CVC, the %CVCmax-change in esophageal temperature (delta T(es)) curve was shifted to the right in the older men (effective delta T(es) associated with 50% CVC response for young, 0.22 +/- 0.04 and 0.39 +/- 0.04 degrees C and for older, 0.73 +/- 0.04 and 0.85 +/- 0.04 degrees C at control and BT sites, respectively). BT had no interactive effect on this age difference, suggesting a lack of involvement of the VC system in the attenuated CVC response of individuals over the age of 60 yr. Additionally, increases in skin vascular conductance were quantitatively compared by measuring increases in total forearm vascular conductance (FVC, restricted to the forearm skin under these conditions). After the initial approximately 0.2 degrees C increase in T(es), FVC was 40-50% lower in the older men (P < 0.01) for the remainder of the exercise. Decreased active vasodilator sensitivity to increasing core temperature, coupled with

  3. The effect of decreased developer activity on patient exposure

    International Nuclear Information System (INIS)

    Burns, C.B.; Turner, G.W.

    1983-01-01

    Overexposing and underdeveloping a radiographic image is not a common practice, but it has been observed to occur as a result of poor processing protocols. This study discovered that, as a result of decreased developer activity, the patient exposure could be three times as great as it would be under normal conditions

  4. DNA damage and decrease of cellular oxidase activity in piglet ...

    African Journals Online (AJOL)

    DNA damage and decrease of cellular oxidase activity in piglet sertoli cells exposed to gossypol. Ming Zhang, Hui Yuan, Zuping He, Liyun Yuan, Jine Yi, Sijun Deng, Li Zhu, Chengzhi Guo, Yin Lu, Jing Wu, Lixin Wen, Qiang Wei, Liqun Xue ...

  5. Decreased antitoxic activities among children with clinical episodes of malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; McKay, V; N'Jie, R

    1998-01-01

    Healthy Gambian children, children with clinical Plasmodium falciparum malaria, and children with asymptomatic P. falciparum infections were studied to investigate whether antitoxic activities may contribute to protection against malarial symptoms. Markers of inflammatory reactions, soluble tumor...... necrosis factor receptor I, and C-reactive protein were found in high concentrations in children with symptomatic P. falciparum malaria compared with levels in children with asymptomatic P. falciparum infections or in healthy children, indicating that inflammatory reactions are induced only in children...... decreased capacity to block induction of LAL activation by P. falciparum exoantigen. The decreased blocking activity was restored in the following dry season, when the children had no clinical malaria. Symptomatic children also had the highest immunoglobulin G (IgG) reactivities to conserved P. falciparum...

  6. Some human activities to decrease public radiation dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Guo Minqiang

    1994-01-01

    The necessity of studying the variations in radiation levels from the balance viewpoint is discussed. Some human activities may increase, while others may decrease, radiation dose to population. In 1988, China's investigation showed that travel by air caused a raise of population collective dose by 3.6 x 10 1 man·Sv, while travel by ship, train and vehicle lead to a drop of 5.36 x 10 2 man·Sv, and that dwellings of coal cinder brick decreased collective dose by 3.5 x 10 3 man·Sv, while buildings of reinforced concrete structure increased collective dose by 3.7 x 10 3 man·Sv. It is inadequate to only study those activities which may increase radiation levels

  7. Increased physical activity decreases periodontitis risk in men

    International Nuclear Information System (INIS)

    Merchant, Anwar T.; Pitiphat, Waranuch; Rimm, Eric B.; Joshipura, Kaumudi

    2003-01-01

    Background: Increased physical activity improves insulin sensitivity and glucose metabolism, and may therefore affect incidence of periodontitis. Methods: We studied the association of physical activity, walking and periodontitis in 39,461 male, US based, health professionals, 40-75 years old at baseline, more than half of whom were dentists, being followed up continuously since 1986. Participants were free of periodontitis, coronary heart disease and stroke at the start of follow-up. Physical activity and periodontitis were measured by validated questionnaires (expressed in metabolic equivalents - METs); the first report of professionally diagnosed periodontitis was considered a case. Results: Periodontitis risk decreased by 3% for every 10-MET increase in average physical activity after adjustment for age, smoking, diabetes, BMI, alcohol consumption and total calories (RR = 0.97; 95% CI: 0.95-0.99). The inverse trend remained significant in the categorical analysis. Compared to men in the lowest quintile of physical activity, those in the highest quintile had a 13% lower risk of periodontitis (RR = 0.87; 95% CI: 0.76-1.01, p-value, test for trend = 0.02). In a sub-sample of men with radiographs (n = 137) the physically active had less average bone loss (β = -0.29, p-value = 0.03) after multivariate adjustment compared to those inactive. Conclusions: In this large-scale prospective study, we found an inverse, linear association between sustained physical activity and periodontitis independent of known risk factors. The benefits of a physically active lifestyle may extend to periodontal health

  8. Mineral water 222 Rn activity decrease due to consumption habits

    International Nuclear Information System (INIS)

    Cipriani, Moacir; Taddei, Maria Helena Tirollo; Silva, Nivaldo Carlos da

    2001-01-01

    Mineral waters from the Pocos de Caldas Plateau springs, an elevated region with high natural radioactivity, in the State of Minas Gerais, Brazil, have significant 222 Rn concentration on site. The highest concentration in the waters are from: Fonte Villela - Aguas da Prata (∼ 1000 Bql -1 ); Fonte Grande Hotel - Pocinhos do Rio Verde (∼ 400 Brq -1 ) and Fonte CNEN Lab - Pocos de Caldas (∼ 290 Bql -1 ). These waters are used by the population as drinking water and due to consumption habits, can lead to internal doses above accepted limits for the public. This work deals with the decrease of 222 Rn activity in mineral waters fro two different popular consumption habits, and with the adult effective dose equivalent reduction due to water consumption habits. It has been found that the estimated dose based on the biokinetic Crawford-Brown model, can be one fourth of dose based on 222 Rn activity on site. (author)

  9. Active Intervention Can Decrease Burnout In Ed Nurses.

    Science.gov (United States)

    Wei, Rong; Ji, Hong; Li, Jianxin; Zhang, Liyao

    2017-03-01

    The aim of this study was to evaluate whether active intervention can decrease job burnout and improve performance among ED nurses. This study was carried out in the emergency departments of 3 hospitals randomly selected from 8 comprehensive high-level hospitals in Jinan, China. A total of 102 nurses were enrolled and randomly divided into control and intervention groups. For 6 months, nurses in intervention groups were treated with ordinary treatment plus comprehensive management, whereas nurses in the control group were treated with ordinary management, respectively. Questionnaires were sent and collected at baseline and at the end of the study. The Student t test was used to evaluate the effect of comprehensive management in decreasing burnout. All ED nurses showed symptoms of job burnout at different levels. Our data indicated that comprehensive management significantly decreased emotional exhaustion and depersonalization (P burnout in ED nurses and contribute to relieving work-related stress and may further protect against potential mental health problems. Copyright © 2016 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.

  10. Why does serotonergic activity drastically decrease during REM sleep?

    Science.gov (United States)

    Sato, Kohji

    2013-10-01

    Here, I postulate two hypotheses that can explain the missing link between sleep and the serotonergic system in terms of spine homeostasis and memory consolidation. As dendritic spines contain many kinds of serotonin receptors, and the activation of serotonin receptors generally increases the number of spines in the cortex and hippocampus, I postulate that serotonin neurons are down-regulated during sleep to decrease spine number, which consequently maintains the total spine number at a constant level. Furthermore, since synaptic consolidation during REM sleep needs long-term potentiation (LTP), and serotonin is reported to inhibit LTP in the cortex, I postulate that serotonergic activity must drastically decrease during REM sleep to induce LTP and do memory consolidation. Until now, why serotonergic neurons show these dramatic changes in the sleep-wake cycle remains unexplained; however, making these hypotheses, I can confer physiological meanings on these dramatic changes of serotonergic neurons in terms of spine homeostasis and memory consolidation. Copyright © 2013. Published by Elsevier Ltd.

  11. Decreased dopamine activity predicts relapse in methamphetamine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Wang G. J.; Wang, G.-J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-20

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  12. Decreased dopamine activity predicts relapse in methamphetamine abusers

    International Nuclear Information System (INIS)

    Wang, G.J.; Smith, L.; Volkow, N.D.; Telang, F.; Logan, J.; Tomasi, D.; Wong, C.T.; Hoffman, W.; Jayne, M.; Alia-Klein, N.; Thanos, P.; Fowler, J.S.

    2011-01-01

    Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and ( 11 C)raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

  13. Physically active lifestyle does not decrease the risk of fattening.

    Directory of Open Access Journals (Sweden)

    Klaas R Westerterp

    Full Text Available BACKGROUND: Increasing age is associated with declining physical activity and a gain in fat mass. The objective was to observe the consequence of the age-associated reduction in physical activity for the maintenance of energy balance as reflected in the fat store of the body. METHODOLOGY/PRINCIPAL FINDINGS: Young adults were observed over an average time interval of more than 10 years. Physical activity was measured over two-week periods with doubly labeled water and doubly labeled water validated triaxial accelerometers, and body fat gain was measured with isotope dilution. There was a significant association between the change in physical activity and the change in body fat, where a high initial activity level was predictive for a higher fat gain. CONCLUSION/SIGNIFICANCE: The change from a physically active to a more sedentary routine does not induce an equivalent reduction of energy intake and requires cognitive restriction to maintain energy balance.

  14. Insulin-induced decrease in protein phosphorylation in rat adipocytes not explained by decreased A-kinase activity

    International Nuclear Information System (INIS)

    Egan, J.J.; Greenberg, A.S.; Chang, M.K.; Londos, C.

    1987-01-01

    In isolated rat adipocytes, insulin inhibits lipolysis to a greater extent than would be predicted by the decrease in (-/+)cAMP activity ratio of cAMP-dependent protein kinase [A-kinase], from which it was speculated that insulin promotes the dephosphorylation of hormone-sensitive lipase. They have examined the phosphorylation state of cellular proteins under conditions of varying A-kinase activities in the presence and absence of insulin. Protein phosphorylation was determined by SDS-PAGE electrophoresis of extracts from 32 P-loaded cells; glycerol and A-kinase activity ratios were measured in the cytosolic extracts from control, non-radioactive cells. Increased protein phosphorylation in general occurred over the same range of A-kinase activity ratios, 0.1-0.3, associated with increased glycerol release. The insulin-induced decrease in lipolysis was associated with a decrease in the 32 P content of several proteins, an effect not explained by the modest reduction in A-kinase activity by insulin. This effect of insulin on protein phosphorylation was lost as the A-kinase activity ratios exceeded 0.5. The results suggest that insulin promotes the dephosphorylation of those adipocyte proteins which are subject to phosphorylation by A-kinase

  15. Decrease in gamma-band activity tracks sequence learning

    Science.gov (United States)

    Madhavan, Radhika; Millman, Daniel; Tang, Hanlin; Crone, Nathan E.; Lenz, Fredrick A.; Tierney, Travis S.; Madsen, Joseph R.; Kreiman, Gabriel; Anderson, William S.

    2015-01-01

    Learning novel sequences constitutes an example of declarative memory formation, involving conscious recall of temporal events. Performance in sequence learning tasks improves with repetition and involves forming temporal associations over scales of seconds to minutes. To further understand the neural circuits underlying declarative sequence learning over trials, we tracked changes in intracranial field potentials (IFPs) recorded from 1142 electrodes implanted throughout temporal and frontal cortical areas in 14 human subjects, while they learned the temporal-order of multiple sequences of images over trials through repeated recall. We observed an increase in power in the gamma frequency band (30–100 Hz) in the recall phase, particularly in areas within the temporal lobe including the parahippocampal gyrus. The degree of this gamma power enhancement decreased over trials with improved sequence recall. Modulation of gamma power was directly correlated with the improvement in recall performance. When presenting new sequences, gamma power was reset to high values and decreased again after learning. These observations suggest that signals in the gamma frequency band may play a more prominent role during the early steps of the learning process rather than during the maintenance of memory traces. PMID:25653598

  16. Stereotypic wheel running decreases cortical activity in mice

    Science.gov (United States)

    Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

    2016-01-01

    Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

  17. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder.

    Science.gov (United States)

    Demir, Süleyman; Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-07-01

    Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (pactivity may have neuroprotective effects in patients with PTSD.

  18. Regular sports activities decrease the risk of venous thrombosis

    NARCIS (Netherlands)

    van Stralen, K. J.; le Cessie, S.; Rosendaal, F. R.; Doggen, C. J. M.

    2007-01-01

    BACKGROUND: Stasis of the blood has been postulated as a major cause of venous thrombosis. However, little is known about the effect of stimulating the blood flow in order to prevent venous thrombosis through, for example, sports activities. OBJECTIVES: In a large population-based case-control study

  19. Immune activation is associated with decreased thymic function in ...

    African Journals Online (AJOL)

    Background: Reduced thymic function causes poor immunological reconstitution in human immunodeficiency virus (HIV)-positive patients on combined antiretroviral therapy (cART). The association between immune activation and thymic function in asymptomatic HIVpositive treatment-naive individuals has thus far not been ...

  20. Physical activity may decrease the likelihood of children developing constipation.

    Science.gov (United States)

    Seidenfaden, Sandra; Ormarsson, Orri Thor; Lund, Sigrun H; Bjornsson, Einar S

    2018-01-01

    Childhood constipation is common. We evaluated children diagnosed with constipation, who were referred to an Icelandic paediatric emergency department, and determined the effect of lifestyle factors on its aetiology. The parents of children who were diagnosed with constipation and participated in a phase IIB clinical trial on laxative suppositories answered an online questionnaire about their children's lifestyle and constipation in March-April 2013. The parents of nonconstipated children that visited the paediatric department of Landspitali University Hospital or an Icelandic outpatient clinic answered the same questionnaire. We analysed responses regarding 190 children aged one year to 18 years: 60 with constipation and 130 without. We found that 40% of the constipated children had recurrent symptoms, 27% had to seek medical attention more than once and 33% received medication per rectum. The 47 of 130 control group subjects aged 10-18 were much more likely to exercise more than three times a week (72%) and for more than a hour (62%) than the 26 of 60 constipated children of the same age (42% and 35%, respectively). Constipation risk factors varied with age and many children diagnosed with constipation had recurrent symptoms. Physical activity may affect the likelihood of developing constipation in older children. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. Educational level and decreases in leisure time physical activity: predictors from the longitudinal GLOBE study

    NARCIS (Netherlands)

    M. Droomers (Mariël); C.Th.M. Schrijvers (Carola); J.P. Mackenbach (Johan)

    2001-01-01

    textabstractSTUDY OBJECTIVE: This study describes educational differences in decreases in leisure time physical activity among an adult, physically active population and additionally attempts to identify predictors of these differences from information on health status

  2. Decreased ADAMTS 13 Activity is Associated With Disease Severity and Outcome in Pediatric Severe Sepsis

    Science.gov (United States)

    Lin, Jainn-Jim; Chan, Oi-Wa; Hsiao, Hsiang-Ju; Wang, Yu; Hsia, Shao-Hsuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Decreased ADAMTS 13 activity has been reported in severe sepsis and in sepsis-induced disseminated intravascular coagulation. This study aimed to investigate the role of ADAMTS 13 in different pediatric sepsis syndromes and evaluate its relationship with disease severity and outcome. We prospectively collected cases of sepsis treated in a pediatric intensive care unit, between July 2012 and June 2014 in Chang Gung Children's Hospital in Taoyuan, Taiwan. Clinical characteristics and ADAMTS-13 activity were analyzed. All sepsis syndromes had decreased ADAMTS 13 activity on days 1 and 3 of admission compared to healthy controls. Patients with septic shock had significantly decreased ADAMTS 13 activity on days 1 and 3 compared to those with sepsis and severe sepsis. There was a significant negative correlation between ADAMTS 13 activity on day 1 and day 1 PRISM-II, PELOD, P-MOD, and DIC scores. Patients with mortality had significantly decreased ADAMTS 13 activity on day 1 than survivors, but not on day 3. Different pediatric sepsis syndromes have varying degrees of decreased ADAMTS 13 activity. ADAMTS 13 activity is strongly negatively correlated with disease severity of pediatric sepsis syndrome, whereas decreased ADAMTS 13 activity on day 1 is associated with increased risk of mortality. PMID:27100422

  3. Solar activity associated with an unusual series of microwave flux decreases

    International Nuclear Information System (INIS)

    Sawyer, C.

    1976-01-01

    East-limb passage of an activity complex in the spring of 1974 was accompanied by a remarkable series of microwave flux decreases. Within an interval of four days, two post-burst decreases and five 'absorption' events occurred, along with two oscillations. Hα patrol films and a spectrogram show a surge and flare sprays with an unusually large velocity of approach at the time of the first post-burst decrease. Two other 'absorption' events were loosely associated with prominence activations, but no outstanding Hα activity was seen at the time of the oscillations. These observations, along with published data, show that the flux decreases followed only flares that lay westward of the major microwave source; ejections from this location would likely have overlain the source while the region was near the east limb. Absorption by flare-ejected material is a plausible, though not exclusive, explanation of these events. (author)

  4. Glucose-6-phosphate dehydrogenase activity decreases during storage of leukoreduced red blood cells

    NARCIS (Netherlands)

    Peters, Anna L.; van Bruggen, Robin; de Korte, Dirk; van Noorden, Cornelis J. F.; Vlaar, Alexander P. J.

    2016-01-01

    During storage, the activity of the red blood cell (RBC) antioxidant system decreases. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection against oxidative stress by producing NADPH. G6PD function of RBC transfusion products is reported to remain stable during storage, but activity

  5. Enhancement of the Electrocatalytic Activity of Gold Nanoparticles via Anodic Treatment and the Decrease of the Enhanced Activity with Aging

    International Nuclear Information System (INIS)

    Jo, Kyung Min; Kang, Hyun Ju; Yang, Hae Sik

    2011-01-01

    We have recently shown that the electrocatalytic activity of Au nanoparticles (AuNPs) can be enhanced via NaBH 4 treatment and cathodic treatment and that the enhanced activity slowly decreases with aging. We have also demonstrated that the electrocatalytic activity of the AuNPs freshly prepared by electrochemical or chemical reduction slowly decreases with aging in both air and solution. Likewise, the electrocatalytic activity of anodically treated Au electrodes or AuNPs might change with aging. Herein, we report that the electrocatalytic activity of long-aged AuNPs can be enhanced via anodic treatment and that the enhanced electrocatalytic activity decreases with aging in air. The change in the electrocatalytic activity of AuNPs was evaluated by comparing cyclic voltammograms for the electrooxi-dation of hydrogen peroxide (H 2 O 2 ) and formic acid

  6. Correlations decrease with propagation of spiking activity in the mouse barrel cortex

    Directory of Open Access Journals (Sweden)

    Gayathri Nattar Ranganathan

    2011-05-01

    Full Text Available Propagation of suprathreshold spiking activity through neuronal populations is important for the function of the central nervous system. Neural correlations have an impact on cortical function particularly on the signaling of information and propagation of spiking activity. Therefore we measured the change in correlations as suprathreshold spiking activity propagated between recurrent neuronal networks of the mammalian cerebral cortex. Using optical methods we recorded spiking activity from large samples of neurons from two neural populations simultaneously. The results indicate that correlations decreased as spiking activity propagated from layer 4 to layer 2/3 in the rodent barrel cortex.

  7. Decreased medial prefrontal cortex activation during self-referential processing in bipolar mania.

    Science.gov (United States)

    Herold, Dorrit; Usnich, Tatiana; Spengler, Stephanie; Sajonz, Bastian; Bauer, Michael; Bermpohl, Felix

    2017-09-01

    Patients with bipolar disorder in mania exhibit symptoms pointing towards altered self-referential processing, such as decreased self-focus, flight of ideas and high distractibility. In depression, the opposite pattern of symptoms has been connected to increased activation of medial prefrontal cortex (mPFC) during self-referential processing. In this study, we hypothesized that (1) patients with mania will exhibit decreased activation in the mPFC during self-referential processing and (2) will be more alexithymic and that levels of alexithymia will correlate negatively with mPFC activation. The neural response to standardized pictures was compared in 14 patients with bipolar I disorder in mania to 14 healthy controls using blood oxygen level dependent contrast magnetic resonance imaging. Participants were asked to indicate with button press during the scanning session for each picture whether the pictures personally related to them or not. Toronto alexithymia scale (TAS) scores were recorded from all participants. In the group analysis, patients with mania exhibited decreased activation in a predefined region of interest in the mPFC during self-referential processing compared to healthy controls. Patients with mania showed significantly higher levels of alexithymia, attributable to difficulties in identifying and describing emotions. Activation in the mPFC correlated negatively with levels of alexithymia. Results presented here should be replicated in a larger group, potentially including unmedicated patients. The finding of decreased mPFC activation during self-referential processing in mania may reflect decreased self-focus and high distractibility. Support for this view comes from the negative correlation between higher alexithymia scores and decreased mPFC activation. These findings represent an opposite clinical and neuroimaging pattern to findings in depression. Copyright © 2017. Published by Elsevier B.V.

  8. Prenatal Protein Malnutrition Decreases KCNJ3 and 2DG Activity in Rat Prefrontal Cortex

    Science.gov (United States)

    Amaral, A.C.; Jakovcevski, M.; McGaughy, J.A.; Calderwood, S.K.; Mokler, D.J.; Rushmore, R.J.; Galler, J.R.; Akbarian, S.A.; Rosene, D.L.

    2014-01-01

    Prenatal protein malnutrition (PPM) in rats causes enduring changes in brain and behavior including increased cognitive rigidity and decreased inhibitory control. A preliminary gene microarray screen of PPM rat prefrontal cortex (PFC) identified alterations in KCNJ3 (GIRK1/Kir3.1), a gene important for regulating neuronal excitability. Follow-up with polymerase chain reaction and Western blot showed decreased KCNJ3 expression in PFC, but not hippocampus or brainstem. To verify localization of the effect to the PFC, baseline regional brain activity was assessed with 14C-2-deoxyglucose. Results showed decreased activation in PFC but not hippocampus. Together these findings point to the unique vulnerability of the PFC to the nutritional insult during early brain development, with enduring effects in adulthood on KCNJ3 expression and baseline metabolic activity. PMID:25446346

  9. Relationships among nocturnal jaw muscle activities, decreased esophageal pH, and sleep positions.

    Science.gov (United States)

    Miyawaki, Shouichi; Tanimoto, Yuko; Araki, Yoshiko; Katayama, Akira; Imai, Mikako; Takano-Yamamoto, Teruko

    2004-11-01

    The purpose of this study was to examine the relationships among nocturnal jaw muscle activities, decreased esophageal pH, and sleep positions. Twelve adult volunteers, including 4 bruxism patients, participated in this study. Portable pH monitoring, electromyography of the temporal muscle, and audio-video recordings were conducted during the night in the subjects' homes. Rhythmic masticatory muscle activity (RMMA) episodes were observed most frequently, with single short-burst episodes the second most frequent. The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. Both the electromyography and the decreased esophageal pH episodes were most frequently observed in the supine position. These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.

  10. Soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2

    DEFF Research Database (Denmark)

    Gjørlund, Michelle D.; Carlsen, Eva Maria Meier; Kønig, Andreas Bay

    2017-01-01

    Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent ...

  11. Causes of decreased activity of daily life in elderly patients who need daily living care.

    Science.gov (United States)

    Yoshino, Hiroshi; Sakurai, Takashi; Hasegawa, Kazuo; Yokono, Koichi

    2011-07-01

    The causes of decreased activity of daily life (ADL) in elderly patients include cerebrovascular diseases, bone fracture by falls, and dementia. The present study was conducted among elderly patients with decreased ADL who were hospitalized in nursing wards in order to investigate the causes of becoming early bedridden and to determine precautionary measures against decreased ADL. The study subjects were 224 elderly patients with decreased ADL (mean age: 83.3 ± 8.0 years) and 49 outpatients without decreased ADL (mean age: 76.8 ± 5.3 years). Current age, age at the start of ADL decrease, medical history and history of smoking were investigated. In the groups with decreased ADL, current age and the age of becoming bedridden in non-diabetic versus diabetic groups were 84.7 ± 7.9 versus 80.3 ± 7.5 and 82.7 ± 8.3 versus 77.6 ± 8.0 years, respectively, both showing significantly lower values in the diabetic group (P bedridden. Diabetic patients with smoking habit were significantly younger than diabetic and non-diabetic patients without smoking habit. Sex difference, smoking habit and presence of diabetes mellitus are independent risk factors of becoming early bedridden. Therefore, the major targets of medical care among elderly should be diabetic men with a smoking habit to lower the risks of decreased ADL. © 2011 Japan Geriatrics Society.

  12. Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD

    Directory of Open Access Journals (Sweden)

    Chen Yanwei

    2012-03-01

    Full Text Available Abstract Background Histone deacetylase (HDAC is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD, while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail. Methods HDAC activities in peripheral blood mononuclear cells (PBMC were investigated in patients with stable COPD (n = 26, non-smoking controls (n = 13, and smoking controls (n = 10, respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8 levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines. Results Compared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg, p Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities. Conclusion In patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.

  13. Proliferation activity and radiosensitivity of CFU-S in their decreased compartments in continuously irradiated rats

    International Nuclear Information System (INIS)

    Kalina, I.; Vacek, A.; Brezani, P.

    1984-01-01

    Effects of the continuous irradiation (0.25 Gy/day) on proliferation activity and radiosensitivity (D 0 ) of CFU-S were studied in rats after accumulated doses of 1.75 Gy and 15 Gy, resp. The proliferation activity of CFU-S in continuously irradiated groups was increased 4 - 5 fold compared with the control group. D 0 values for CFU-S in their decreased compartments were not changed after long-term irradiation compared with the controls. (author)

  14. Educational level and decreases in leisure time physical activity: predictors from the longitudinal GLOBE study

    OpenAIRE

    Droomers, Mariël; Schrijvers, Carola; Mackenbach, Johan

    2001-01-01

    STUDY OBJECTIVE—This study describes educational differences in decreases in leisure time physical activity among an adult, physically active population and additionally attempts to identify predictors of these differences from information on health status and individual and environmental factors.
DESIGN—Prospective population based study. Baseline measurement were carried out in 1991 and follow up in 1997.
SETTING—South eastern part of the Netherlands.
PARTICIPANTS—The study included 3793 su...

  15. Sympathetic nervous activity decreases during head-down bed rest but not during microgravity

    DEFF Research Database (Denmark)

    Christensen, Niels J; Heer, Martina; Ivanova, Krassimira

    2005-01-01

    We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy......, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P

  16. Recurrent forbush decreases and the relationship between active regions and M regions

    International Nuclear Information System (INIS)

    Shah, G.N.; Kaul, C.L.; Razdan, H.; Bemalkhedkar, M.M.

    1978-01-01

    Recurrent Forbush decreases and recurrent geomagnetic disturbances have been attributed to the solar M regions, which are sources of high-velocity solar plasma streams. A study of recurrent Forbush decreases for the period 1966--1975 has been made to examine any possible relationship of M regions with solar active regions. It is shown that at the onset of the recurrent Forbush decrease at the earth there is a high probability of encountering a class of active regions at the central meridian of the sun which give rise to flares of importance > or =2B/3N. These active regions are found to be long lasting and to have large areas as well as high Hα intensities. Other active regions, producing flares of lower importance, are distributed randomly on the sun with respect to the onset of a recurrent Forbush decrease. By using the quasi-radial hypervelocity approximation the base of the leading edge of the high-velocity stream at the onset of a recurrent Forbush decrease at the earth is traced to the solar longitude about 40 0 west of the central meridan. From these results it is deduced that M regions are located preferentially to the west of long-lasting magnetically complex active regions. Earlier studies of the identification of the M regions on the sun have been reexamined and shown to conform to this positional relationship. A possible mechanism of the development of an M region to the west of the long-lasting magnetically complex active region is also discussed

  17. Recurrent Forbush decreases and relationship between active regions and M-regions

    International Nuclear Information System (INIS)

    Shah, G.N.; Kaul, C.L.; Razdan, H.; Bemalkhedkar, M.M.

    1977-01-01

    Recurrent Forbush decreases and recurrent geomagnetic disturbances have been attributed to the solar M-regions, which are sources of high velocity solar plasma streams. A study of recurrent Forbush decreases for the period 1966-75 has been made to examine any possible relationship of M-regions with solar active regions. It is shown that at the onset of the recurrent Forbush decrease at earth, there is a high probability of encountering a class of active regions at central meridian of the sun which give rise to flares of importance >= 28/3N. These active regions are found to be long-lasting and to have large areas as well as high Hsub(α)-intensities. Other active regions, producing flares of only lower importance, are distributed randomly on the sun with respect to the onset of a recurrent Forbush decrease. Using the quasiradial hypervelocity approximation, the base of the leading edge of the high velocity stream, at the onset of a recurrent Forbush decrease at earth, is traced to the solar longitude about 40 deg West of the central meridian. From these results, it is deduced that M-regions are located preferentially to the West of long-lasting, magnetically complex active regions. Earlier studies of the identification of the M-regions on the sun have been re-examined and shown to conform to this positional relationship. A possible mechanism of the development of an M-region to the West of the long-lasting magnetically complex active region is also discussed. (author)

  18. Rapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior.

    Science.gov (United States)

    Cornil, C A; Dalla, C; Papadopoulou-Daifoti, Z; Baillien, M; Dejace, C; Ball, G F; Balthazart, J

    2005-09-01

    In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior.

  19. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Yiyang, E-mail: yuanyy@ioz.ac.cn [State Key Laboratory of Integrated Management of Pest and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101 (China); Graduate School, Chinese Academy of Sciences, Beijing 100039 (China); Ke Xin, E-mail: xinke@sibs.ac.cn [Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai 200032 (China); Chen Fajun, E-mail: fajunchen@njau.edu.cn [College of Plant Protection, Department of Entomology, Nanjing Agricultural University, Nanjing 210095 (China); Krogh, Paul Henning, E-mail: phk@dmu.dk [Department of Bioscience, University of Aarhus, P.O. Box 314, Vejlsoevej 25, DK-8600 Silkeborg (Denmark); Ge Feng, E-mail: gef@ioz.ac.cn [State Key Laboratory of Integrated Management of Pest and Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101 (China)

    2011-12-15

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed the Bt-rice variety Kemingdao compared to the near-isogenic non-Bt-rice variety Xiushui. This suggests that some Bt-rice varieties may impose environmental stress to collembolans. We emphasize that changes in activity of antioxidant enzymes of non-target organisms are important in understanding the ecological consequences for organisms inhabiting transgenic Bt-rice plantations. - Highlights: > We examine the effects of Bt-rice on Folsomia candida with laboratory test. > The reproduction of F. candida was decreased by two Bt-rice varieties. > Decreased reproduction caused by the differences of varieties or C/N ratio of rice. > The catalase activity was decreased by Bt-rice Kemingdao. > Some Bt-rice may impose environmental stress on NTOs. - The catalase of the collembolan (Folsomia candida) was decreased when fed Bt-rice, Kemingdao.

  20. Decreasing Sports Activity with Increasing Age? Findings from a 20-Year Longitudinal and Cohort Sequence Analysis

    Science.gov (United States)

    Breuer, Christoph; Wicker, Pamela

    2009-01-01

    According to cross-sectional studies in sport science literature, decreasing sports activity with increasing age is generally assumed. In this paper, the validity of this assumption is checked by applying more effective methods of analysis, such as longitudinal and cohort sequence analyses. With the help of 20 years' worth of data records from the…

  1. Fingolimod in active multiple sclerosis: an impressive decrease in Gd-enhancing lesions

    NARCIS (Netherlands)

    Muris, A.H.; Rolf, L.; Damoiseaux, J.; Koeman, E.; Hupperts, R.

    2014-01-01

    Background: Fingolimod is a disease modifying therapy (DMT) in highly active relapsing remitting multiple sclerosis (RRMS), as is natalizumab. Fingolimod decreases annual relapse rates and gadolinium enhancing lesions on MRI as compared to either interferon beta (IFNβ) or placebo. The effect of

  2. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    International Nuclear Information System (INIS)

    Yuan Yiyang; Ke Xin; Chen Fajun; Krogh, Paul Henning; Ge Feng

    2011-01-01

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed the Bt-rice variety Kemingdao compared to the near-isogenic non-Bt-rice variety Xiushui. This suggests that some Bt-rice varieties may impose environmental stress to collembolans. We emphasize that changes in activity of antioxidant enzymes of non-target organisms are important in understanding the ecological consequences for organisms inhabiting transgenic Bt-rice plantations. - Highlights: → We examine the effects of Bt-rice on Folsomia candida with laboratory test. → The reproduction of F. candida was decreased by two Bt-rice varieties. → Decreased reproduction caused by the differences of varieties or C/N ratio of rice. → The catalase activity was decreased by Bt-rice Kemingdao. → Some Bt-rice may impose environmental stress on NTOs. - The catalase of the collembolan (Folsomia candida) was decreased when fed Bt-rice, Kemingdao.

  3. Valsartan Decreases Platelet Activity and Arterial Thrombotic Events in Elderly Patients with Hypertension

    Directory of Open Access Journals (Sweden)

    Fang Wu

    2015-01-01

    Conclusions: AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

  4. Neural correlates of skill acquisition: decreased cortical activity during a serial interception sequence learning task.

    Science.gov (United States)

    Gobel, Eric W; Parrish, Todd B; Reber, Paul J

    2011-10-15

    Learning of complex motor skills requires learning of component movements as well as the sequential structure of their order and timing. Using a Serial Interception Sequence Learning (SISL) task, participants learned a sequence of precisely timed interception responses through training with a repeating sequence. Following initial implicit learning of the repeating sequence, functional MRI data were collected during performance of that known sequence and compared with activity evoked during novel sequences of actions, novel timing patterns, or both. Reduced activity was observed during the practiced sequence in a distributed bilateral network including extrastriate occipital, parietal, and premotor cortical regions. These reductions in evoked activity likely reflect improved efficiency in visuospatial processing, spatio-motor integration, motor planning, and motor execution for the trained sequence, which is likely supported by nondeclarative skill learning. In addition, the practiced sequence evoked increased activity in the left ventral striatum and medial prefrontal cortex, while the posterior cingulate was more active during periods of better performance. Many prior studies of perceptual-motor skill learning have found increased activity in motor areas of the frontal cortex (e.g., motor and premotor cortex, SMA) and striatal areas (e.g., the putamen). The change in activity observed here (i.e., decreased activity across a cortical network) may reflect skill learning that is predominantly expressed through more accurate performance rather than decreased reaction time. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Mean platelet volume is decreased in adults with active lupus disease

    Directory of Open Access Journals (Sweden)

    Guillermo Delgado-García

    Full Text Available ABSTRACT Background: Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE. Mean platelet volume (MPV has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. Objective: We investigated the association between MPV and disease activity in adult patients with SLE. Methods: In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group. Subjects were age- and gender-matched. Results: MPV was significantly decreased with respect to those of inactive patients (7.16 ± 1.39 vs. 8.16 ± 1.50, p = 0.005. At a cutoff level of 8.32 fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r = 0.407, p = 0.001, which in turn is inversely associated with disease activity. Conclusions: In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker.

  6. Mean platelet volume is decreased in adults with active lupus disease.

    Science.gov (United States)

    Delgado-García, Guillermo; Galarza-Delgado, Dionicio Ángel; Colunga-Pedraza, Iris; Borjas-Almaguer, Omar David; Mandujano-Cruz, Ilse; Benavides-Salgado, Daniel; Martínez-Granados, Rolando Jacob; Atilano-Díaz, Alexandro

    Only a few biomarkers are available for assessing disease activity in systemic lupus erythematosus (SLE). Mean platelet volume (MPV) has been recently studied as an inflammatory biomarker. It is currently unclear whether MPV may also play a role as a biomarker of disease activity in adult patients with SLE. We investigated the association between MPV and disease activity in adult patients with SLE. In this retrospective study, we compared two groups of adult patients divided according to disease activity (36 per group). Subjects were age- and gender-matched. MPV was significantly decreased with respect to those of inactive patients (7.16±1.39 vs. 8.16±1.50, p=0.005). At a cutoff level of 8.32fL, MPV has a sensitivity of 86% and a specificity of 41% for the detection of disease activity. A modest positive correlation was found between MPV and albumin (r=0.407, p=0.001), which in turn is inversely associated with disease activity. In summary, MPV is decreased in adult patients with active lupus disease, and positively correlated with albumin, another biomarker of disease activity. Prospective studies are needed to evaluate the prognostic value of this biomarker. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  7. Azolla filiculoides Nitrogenase Activity Decrease Induced by Inoculation with Chlamydomonas sp. †

    Science.gov (United States)

    Habte, Mitiku

    1986-01-01

    Experiments were conducted to determine the influence of Chlamydomonas sp. on nitrogen fixation (C2H2 → C2H4) in Azolla filiculoides and on the nitrogen fixation and growth of free-living Anabaena azollae 2B organisms. Inoculation of azolla medium with Chlamydomonas sp. was associated with decreased nitrogenase activity in A. filiculoides and with increases in the density of a fungal population identified as Acremonium sp. Subsequent inoculation of azolla medium with this fungus was also accompanied by a significant decrease in nitrogenase activity of A. filiculoides. However, the extent of depression of nitrogenase activity was significantly higher when azolla medium was inoculated with Chlamydomonas sp. than when it was inoculated with Acremonium sp. Inoculation of nitrogen-free Stanier medium with either Acremonium sp. or Chlamydomonas sp. did not adversely affect the growth or nitrogenase activity of free-living A. azollae. Decreased nitrogenase activity in A. filiculoides is apparently related to the adverse influence of the green alga and the fungus on the macrosymbiont. The mechanisms that might be involved are discussed. PMID:16347211

  8. The cell-free fetal DNA fraction in maternal blood decreases after physical activity

    DEFF Research Database (Denmark)

    Schlütter, Jacob Mørup; Hatt, Lotte; Bach, Cathrine

    2014-01-01

    of cycling with a pulse-rate of 150 beats per minute. The concentrations of cffDNA (DYS14) and cfDNA (RASSF1A) were assessed using quantitative real-time polymerase chain reaction. RESULTS: The fetal fraction decreased significantly in all participants after physical activity (p decrease varying......OBJECTIVE: If noninvasive prenatal testing using next generation sequencing is to be effective for pregnant women, a cell-free fetal DNA (cffDNA) fraction above 4% is essential unless the depth of sequencing is increased. This study's objective is to determine whether physical activity has...... from 1-17 percentage points. This was due to a significant increase in the concentration of cfDNA (p physical activity. CONCLUSION: When planning the timing of noninvasive...

  9. Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity.

    Science.gov (United States)

    Takayama, S; White, M F; Kahn, C R

    1988-03-05

    The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the function of the insulin receptor was examined in intact hepatoma cells (Fao) and in solubilized extracts purified by wheat germ agglutinin chromatography. Incubation of ortho[32P]phosphate-labeled Fao cells with TPA increased the phosphorylation of the insulin receptor 2-fold after 30 min. Analysis of tryptic phosphopeptides from the beta-subunit of the receptor by reverse-phase high performance liquid chromatography and determination of their phosphoamino acid composition suggested that TPA predominantly stimulated phosphorylation of serine residues in a single tryptic peptide. Incubation of the Fao cells with insulin (100 nM) for 1 min stimulated 4-fold the phosphorylation of the beta-subunit of the insulin receptor. Prior treatment of the cells with TPA inhibited the insulin-stimulated tyrosine phosphorylation by 50%. The receptors extracted with Triton X-100 from TPA-treated Fao cells and purified on immobilized wheat germ agglutinin retained the alteration in kinase activity and exhibited a 50% decrease in insulin-stimulated tyrosine autophosphorylation and phosphotransferase activity toward exogenous substrates. This was due primarily to a decrease in the Vmax for these reactions. TPA treatment also decreased the Km of the insulin receptor for ATP. Incubation of the insulin receptor purified from TPA-treated cells with alkaline phosphatase decreased the phosphate content of the beta-subunit to the control level and reversed the inhibition, suggesting that the serine phosphorylation of the beta-subunit was responsible for the decreased tyrosine kinase activity. Our results support the notion that the insulin receptor is a substrate for protein kinase C in the Fao cell and that the increase in serine phosphorylation of the beta-subunit of the receptor produced by TPA treatment inhibited tyrosine kinase activity in vivo and in vitro. These data suggest that protein kinase C may regulate the function

  10. Decreased electrophysiological activity represents the conscious state of emptiness in meditation

    Science.gov (United States)

    Hinterberger, Thilo; Schmidt, Stephanie; Kamei, Tsutomu; Walach, Harald

    2014-01-01

    Many neuroscientific theories explain consciousness with higher order information processing corresponding to an activation of specific brain areas and processes. In contrast, most forms of meditation ask for a down-regulation of certain mental processing activities while remaining fully conscious. To identify the physiological properties of conscious states with decreased mental and cognitive processing, the electrical brain activity (64 channels of EEG) of 50 participants of various meditation proficiencies was measured during distinct and idiosyncratic meditative tasks. The tasks comprised a wakeful “thoughtless emptiness (TE),” a “focused attention,” and an “open monitoring” task asking for mindful presence in the moment and in the environment without attachment to distracting thoughts. Our analysis mainly focused on 30 highly experienced meditators with at least 5 years and 1000 h of meditation experience. Spectral EEG power comparisons of the TE state with the resting state or other forms of meditation showed decreased activities in specific frequency bands. In contrast to a focused attention task the TE task showed significant central and parietal gamma decreases (p meditation practice did not present those differences significantly. Our findings indicate that a conscious state of TE reached by experienced meditators is characterized by reduced high-frequency brain processing with simultaneous reduction of the low frequencies. This suggests that such a state of meditative conscious awareness might be different from higher cognitive and mentally focused states but also from states of sleep and drowsiness. PMID:24596562

  11. Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression.

    Science.gov (United States)

    Caldieraro, Marco Antonio; Walsh, Samantha; Deckersbach, Thilo; Bobo, William V; Gao, Keming; Ketter, Terence A; Shelton, Richard C; Reilly-Harrington, Noreen A; Tohen, Mauricio; Calabrese, Joseph R; Thase, Michael E; Kocsis, James H; Sylvia, Louisa G; Nierenberg, Andrew A

    2017-11-01

    Activation encompasses energy and activity and is a central feature of bipolar disorder. However, the impact of activation on treatment response of bipolar depression requires further exploration. The aims of this study were to assess the association of decreased activation and sustained remission in bipolar depression and test for factors that could affect this association. We assessed participants with Diagnostic and Statistical Manual of Mental Disorders (4th ed) bipolar depression ( n = 303) included in a comparative effectiveness study of lithium- and quetiapine-based treatments (the Bipolar CHOICE study). Activation was evaluated using items from the Bipolar Inventory of Symptoms Scale. The selection of these items was based on a dimension of energy and interest symptoms associated with poorer treatment response in major depression. Decreased activation was associated with lower remission rates in the raw analyses and in a logistic regression model adjusted for baseline severity and subsyndromal manic symptoms (odds ratio = 0.899; p = 0.015). The manic features also predicted lower remission (odds ratio = 0.934; p bipolar depression. Patients with these features may require specific treatment approaches, but new studies are necessary to identify treatments that could improve outcomes in this population.

  12. Decreased sialidase activity in alveolar macrophages of guinea pigs exposed to coal mine dust.

    Science.gov (United States)

    Terzidis-Trabelsi, H; Lefèvre, J P; Bignon, J; Lambré, C R

    1992-01-01

    The origin of immune dysfunctions that are observed in pneumoconiotic miners still remains unknown. There is evidence that the carbohydrate moiety of membrane glycoconjugates is of primary importance in many functions of immunocompetent cells. The glycosylation, and especially the sialylation level of membrane components of various lymphocyte and macrophage subsets, vary depending on the state of cellular differentiation and activation. Sialidases, which may regulate the amount of sialic acids exposed on the cell membrane, can thus be considered as immunoregulatory enzymes. In this report, the sialidase activity has been measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage 2 months after cessation of exposure. The sialidase activity in the cell-free fluid and in the purified alveolar macrophages showed a 10-fold decrease (p less than 0.001). Kinetic parameters of the enzyme such as Km and optimum pH did not change. This changed activity was specific for sialidase, as two other lysosomal glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged activities. These results suggest the possibility that, by inducing a decreased sialidase activity, exposure to coal mine dust may lead to a modified expression of AM membrane-associated sialic acids giving rise to altered immune functions (i. e., phagocytosis, antigen processing, response to cytokines, etc.). PMID:1396442

  13. Airway Peroxidases Catalyze Nitration of the β2-Agonist Salbutamol and Decrease Its Pharmacological Activity

    OpenAIRE

    Reszka, Krzysztof J.; Sallans, Larry; Macha, Stephen; Brown, Kari; McGraw, Dennis W.; Kovacic, Melinda Butsch; Britigan, Bradley E.

    2011-01-01

    β2-Agonists are the most effective bronchodilators for the rapid relief of asthma symptoms, but for unclear reasons, their effectiveness may be decreased during severe exacerbations. Because peroxidase activity and nitrogen oxides are increased in the asthmatic airway, we examined whether salbutamol, a clinically important β2-agonist, is subject to potentially inactivating nitration. When salbutamol was exposed to myeloperoxidase, eosinophil peroxidase or lactoperoxidase in the presence of hy...

  14. Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

    Science.gov (United States)

    Yang, Yutao; Li, Yueting; Di, Fei; Cui, Jiajun; Wang, Yue; David Xu, Zhi-Qing

    2016-12-20

    Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

  15. Salinity Inhibits Rice Seed Germination by Reducing α-Amylase Activity via Decreased Bioactive Gibberellin Content

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available Seed germination plays important roles in the establishment of seedlings and their subsequent growth; however, seed germination is inhibited by salinity, and the inhibitory mechanism remains elusive. Our results indicate that NaCl treatment inhibits rice seed germination by decreasing the contents of bioactive gibberellins (GAs, such as GA1 and GA4, and that this inhibition can be rescued by exogenous bioactive GA application. To explore the mechanism of bioactive GA deficiency, the effect of NaCl on GA metabolic gene expression was investigated, revealing that expression of both GA biosynthetic genes and GA-inactivated genes was up-regulated by NaCl treatment. These results suggest that NaCl-induced bioactive GA deficiency is caused by up-regulated expression of GA-inactivated genes, and the up-regulated expression of GA biosynthetic genes might be a consequence of negative feedback regulation of the bioactive GA deficiency. Moreover, we provide evidence that NaCl-induced bioactive GA deficiency inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression. Additionally, exogenous bioactive GA rescues NaCl-inhibited seed germination by enhancing α-amylase activity. Thus, NaCl treatment reduces bioactive GA content through promotion of bioactive GA inactivation, which in turn inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression.

  16. Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

    Science.gov (United States)

    Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

    2013-04-01

    While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p physical activity reduces cancer risk (p physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

  17. NFKB activity decreased in BALB/c mice with high fat diet and fructose

    Science.gov (United States)

    Nur'aini, Farida Dewi; Rahayu, Sri; Rifa'i, Muhaimin

    2017-05-01

    Excessive consumption of fat and fructose leads to obesity due to lipid accumulation. The excessive lipid causes hypertrophy in the adipocytes which lead to cell death. Consequently, dead adipocytes will produce adipokines, which cause macrophages and lymphocytes to infiltrate into the adipose tissue, elevating pro-inflammatory cytokines, thus triggering the production of pro-inflammatory cytokines through NFκB activity. Elicited soybeans extract (ESE) with bacteria and light contain Glyceollin and Isoflavones, which inhibit the activation of NFKB and reduce plasma cholesterol levels by upregulating cholesterol metabolism. This study aimed to analyze the effect of ESE against the relative number of CD4+ NFκB+ cells in BALB/c mice spleen after administrated by high-fat diet food and fructose (HFD) for 20 weeks. Mice were given orally with ESE after administrated by HFD at dose 78 mg/kgBW (D1), 104 mg/kgBW (D2), and 130 mg/kgBW (D3) for 4 weeks. This study also used positive control (HFD mice model without ESE treatment) and normal mice. Identification of NFKB activation was conducted using Flowcytometry analytical methods. Our result indicated that ESE could decrease significantly activation of NFκB in CD4 cell compare than positive control. The optimum dose that can decrease the relative number of CD4+ NFκB+ cells is dose 3.

  18. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

    Science.gov (United States)

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2016-02-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

  19. Decrease in the cytosolic NADP+-dependent isocitrate dehydrogenase activity through porcine sperm capacitation.

    Science.gov (United States)

    Katoh, Yuki; Tamba, Michiko; Matsuda, Manabu; Kikuchi, Kazuhiro; Okamura, Naomichi

    2018-02-26

    In order to understand the molecular mechanisms involved in the sperm capacitation, we have identified the proteins tyrosine-phosphorylated during the capacitation especially in conjunction with the regulation of the levels of reactive oxygen species (ROS) in sperm. In the present study, the effects of the tyrosine phosphorylation of cytosolic NADP + -dependent isocitrate dehydrogenase (IDPc) on its catalytic activity and on the levels of ROS in sperm have been studied. The tyrosine phosphorylated IDPc showed a significantly lowered enzymatic activity. The immunocytochemical analyses using the highly specific antisera against IDPc revealed that IDPc was mainly localized to the principal piece of the porcine sperm flagellum. As IDPc is one of the major NADPH regenerating enzymes in porcine sperm, it is strongly suggested that the decrease in IDPc activity is involved in the increased levels of ROS, which results in the induction of hyperactivated flagellar movement and capacitation. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity

    DEFF Research Database (Denmark)

    Heftdal, Line Dam; Stengaard-Pedersen, Kristian; Ørnbjerg, Lykke Midtbøll

    2017-01-01

    internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients...... from baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved......Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen...

  1. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    Science.gov (United States)

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Increased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer's disease.

    LENUS (Irish Health Repository)

    Ewers, Michael

    2012-02-01

    The enzyme beta-secretase (BACE1) is essentially involved in the production of cerebral amyloidogenic pathology in Alzheimer\\'s disease (AD). The measurement of BACE1 activity in cerebrospinal fluid (CSF) has been reported, which may render CSF measurement of BACE1 a potential biomarker candidate of AD. In order to investigate whether BACE1 protein activity is correlated with regional brain atrophy in AD, we investigated the association between CSF levels of BACE1 and MRI-assessed hippocampus volume in patients with AD (n = 30). An increase in CSF-BACE1 activity was associated with decreased left and right hippocampus volume corrected for global head volume in the AD patients. Boot-strapped regression analysis showed that increased CSF levels of BACE1 activity were associated with increased CSF concentration of total tau but not amyloid-beta1-42 in AD. White matter hyperintensities did not influence the results. BACE1 activity and protein levels were significantly increased in AD compared to 19 elderly healthy controls. Thus, the CSF biomarker candidate of BACE1 activity was associated with hippocampus atrophy in AD in a robust manner and may reflect neurotoxic amyloid-beta-related processes.

  3. Decreased plasma ADAMTS-13 activity as a predictor of postoperative bleeding in cyanotic congenital heart disease

    Directory of Open Access Journals (Sweden)

    Rosangela P.S. Soares

    2013-04-01

    Full Text Available OBJECTIVE: To analyze the preoperative plasma antigenic concentration and activity of von Willebrand factor and its main cleaving protease ADAMTS-13 in pediatric patients with cyanotic congenital heart disease undergoing surgical treatment and investigate possible correlations with postoperative bleeding. METHODS: Plasma antigenic concentrations (von Willebrand factor:Ag and ADAMTS-13:Ag were measured using enzyme-linked immunoassays. Collagen-binding assays were developed to measure biological activities (von Willebrand factor:collagen binding and ADAMTS-13 activity. The multimeric structure of von Willebrand factor was analyzed using Western immunoblotting. Demographic, diagnostic, and general and specific laboratory data and surgery-related variables were subjected to univariate, bivariate, and multivariate analysis for the prediction of postoperative bleeding. RESULTS: Forty-eight patients were enrolled, with ages ranging from 9 months to 7.6 years (median 2.5 years. The plasma concentrations of von Willebrand factor:Ag and ADAMTS-13:Ag were decreased by 65 and 82%, respectively, in the patients compared with the controls (p<0.001. An increased density of low-molecular-weight fractions of von Willebrand factor, which are suggestive of proteolytic degradation (p = 0.0081, was associated with decreased ADAMTS-13 activity, which was likely due to ADAMTS-13 consumption (71% of controls, p = 0.0029 and decreased von Willebrand factor:collagen binding (76% of controls, p = 0.0004. Significant postoperative bleeding occurred in 13 patients. The preoperative ADAMTS-13 activity of <64.6% (mean level for the group, preoperative activated partial thromboplastin time, and the need for cardiopulmonary bypass were characterized as independent risk factors for postoperative bleeding, with respective hazard ratios of 22.35 (95% CI 1.69 to 294.79, 1.096 (95% CI 1.016 to 1.183, and 37.43 (95% CI 1.79 to 782.73. CONCLUSION: Low plasma ADAMTS-13

  4. Upregulating Nonneuronal Cholinergic Activity Decreases TNF Release from Lipopolysaccharide-Stimulated RAW264.7 Cells

    Directory of Open Access Journals (Sweden)

    Yi Lv

    2014-01-01

    Full Text Available Nonneuronal cholinergic system plays a primary role in maintaining homeostasis. It has been proved that endogenous neuronal acetylcholine (ACh could play an anti-inflammatory role, and exogenous cholinergic agonists could weaken macrophages inflammatory response to lipopolysaccharide (LPS stimulation through activation of α7 subunit-containing nicotinic acetylcholine receptor (α7nAChR. We assumed that nonneuronal cholinergic system existing in macrophages could modulate inflammation through autocrine ACh and expressed α7nAChR on the cells. Therefore, we explored whether LPS continuous stimulation could upregulate the nonneuronal cholinergic activity in macrophages and whether increasing autocrine ACh could decrease TNF release from the macrophages. The results showed that, in RAW264.7 cells incubated with LPS for 20 hours, the secretion of ACh was significantly decreased at 4 h and then gradually increased, accompanied with the enhancement of α7nAChR expression level. The release of TNF was greatly increased from RAW264.7 cells at 4 h and 8 h exposure to LPS; however, it was suppressed at 20 h. Upregulating choline acetyltransferase (ChAT expression through ChAT gene transfection could enhance ACh secretion and reduce TNF release from the infected RAW264. 7cells. The results indicated that LPS stimulation could modulate the activity of nonneuronal cholinergic system of RAW264.7 cells. Enhancing autocrine ACh production could attenuate TNF release from RAW264.7 cells.

  5. The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

    Science.gov (United States)

    Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

    2015-11-01

    The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Pouteria ramiflora extract inhibits salivary amylolytic activity and decreases glycemic level in mice

    Directory of Open Access Journals (Sweden)

    NEIRE M. DE GOUVEIA

    2013-09-01

    Full Text Available In this study, extracts of plant species from the Cerrado biome were assessed in order to find potential inhibitors of human salivary alpha-amylase. The plants were collected and extracts were obtained from leaves, bark, and roots. We performed a preliminary phytochemical analysis and a screening for salivar alpha-amylase inhibitory activity. Only three botanical families (Sapotaceae, Sapindaceae and Flacourtiaceae and 16 extracts showed a substantial inhibition (>75% of alpha-amylase. The ethanolic extracts of Pouteria ramiflora obtained from stem barks and root barks decreased amylolytic activity above 95% at a final concentration of 20 µg/mL. Thus, adult male Swiss mice were treated orally with P. ramiflora in acute toxicity and glycemic control studies. Daily administration with 25, 50 and 100 mg/kg of aqueous extract of P. ramiflora for eight days can reduce significantly body weight and blood glucose level in mice. These data suggest that the crude polar extract of P. ramiflora decreases salivary amylolytic activity while lowering the blood levels of glucose.

  7. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    Directory of Open Access Journals (Sweden)

    Tricia Hubbard-Turner, Erik A. Wikstrom, Sophie Guderian, Michael J. Turner

    2015-09-01

    Full Text Available We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL group, the transected anterior talofibular ligament (ATFL/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011. Daily duration was different between the three running groups (p = 0.048. The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046 while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028 compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019 and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005. The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.

  8. Decreased enzymatic activity of 5,10-methylene tetrahydrofolate reductase affects the development of several diseases

    Directory of Open Access Journals (Sweden)

    Maša Vidmar

    2016-07-01

    Full Text Available The importance of folates in human physiology is well known, as are various pathologies associated with low folate status. Folate deficiency can occur due to low dietary intake, genetic predisposition or treatment with medicines affecting the folate status. The aim of this paper is to explore the importance of determining genetic polymorphisms which influence the levels of biologically active folate. MTHFR is involved in the transformation of 5,10-methylene-THF to 5-methyl-THF. Polymorphisms of the MTHRF gene are associated with decreased enzymatic activity.Only 9.3 % of the population in Slovenia displays full activity of the MTHFR enzyme; these subjects are non-mutated homozygotes (wild-type alleles. In contrast, the average enzymatic activity in subjects with mutated alleles is between 50 and 60 %. MTHFR polymorphism is associated with an increased risk of hyperhomocysteinemia and cardiovascular diseases, neurological disorders and various types of cancer. There is also an increased risk for congenital malformations. Folic acid food fortification was introduced in some countries in order to assure an adequate folate status in the population. However, this approach does not address the decreased activity of MTHFR.Polymorphism in the key enzymes of the folate cycle is common. Determination of the genetic predisposition is therefore plausible in the most vulnerable groups of the population, such as pregnant women and patients receiving medicines influencing the folate cycle in various ways, e.g. 5-fluorouracil, methotrexate and 6-mercaptopurine. Genotyping would allow the identification of patients at high risk for suboptimal folate status.

  9. Why even active people get fatter--the asymmetric effects ofincreasing and decreasing exercise

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Paul T.

    2006-01-06

    Background: Public health policies for preventing obesityneed guidelines for active individuals who are at risk due to exerciserecidivism. Methods: Changes in adiposity were compared to the runningdistances at baseline and follow-up in men and women whose reportedexercise increased (N=4,632 and 1,953, respectively) or decreased (17,280and 5,970, respectively) during 7.7 years of follow-up. Results: PerDelta km/wk, decreases in running distance caused over four-fold greaterweight gain between 0-8 km/wk (slope+-SE, males: -0.068+ -0.005 kg/m2,females: -0.080+-0.01 kg/m2) than between 32-48 km/wk (-0.017+-0.002 and-0.010+-0.005 kg/m2, respectively). In contrast, increases in runningdistance produced the smallest weight losses between 0-8 km/wk andstatistically significant weight loss only above 16 km/wk in males and 32km/wk in females. Above 32 km/wk (30 kcal/kg) in men and 16 km/wk (15kcal/kg) in women, weight loss from increasing exercise was equal to orgreater than weight gained with decreasing exercise, otherwise weightgain exceeded weight loss. Substantial weight gain occurred in runnerswho quit running, which would be mostly retained with resumed activity.Conclusion: Public health recommendations should warn against the risksof irreversible weight gain with exercise cessation. Weight gained due toreductions in exercise below 30 kcal/kg in men and 15 kcal/kg in womenmay not be reversed by resuming prior activity. Current IOM guidelines(i.e., maintain total energy expenditure at 160 percent of basal) agreewith the men s exercise threshold for symmetric weight change withchanging exercise levels.

  10. The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

    Science.gov (United States)

    Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

    2016-04-01

    Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Active Prompting to Decrease Cell Phone Use and Increase Seat Belt Use While Driving

    OpenAIRE

    Clayton, Michael; Helms, Bridgett; Simpson, Cathy

    2006-01-01

    Automobile crashes are the leading cause of death for those aged 3 to 33, with 43,005 (118 per day) Americans killed in 2002 alone. Seat belt use reduces the risk of serious injury in an accident, and refraining from using a cell phone while driving reduces the risk of an accident. Cell phone use while driving increases accident rates, and leads to 2,600 U.S. fatalities each year. An active prompting procedure was employed to increase seat belt use and decrease cell phone use among drivers ex...

  12. Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

    OpenAIRE

    Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2016-01-01

    Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

  13. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    International Nuclear Information System (INIS)

    Carter, M.G.; Shukla, S.D.

    1987-01-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24 degree C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying 32 P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 x 10 -7 M PAF at 37 degree C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for 32 P-phosphoinositides. The percent stimulation of 32 P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage

  14. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  15. Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis

    DEFF Research Database (Denmark)

    Kragstrup, Tue Wenzel; Jalilian, Babak; Hvid, Malene

    2014-01-01

    of arthritis patients to have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity. METHODS: Plasma levels of sCD18 in a study population with 84 SpA patients and matched healthy controls were analyzed with a time resolved......A patients compared with healthy volunteers (P levels in the HLA-B27-positive subgroup (P levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P level of morning...... immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synovial cells (FLS) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMC) was studied with flow cytometry and TRIFMA. RESULTS: Plasma levels of sCD18 were decreased in Sp...

  16. Electronic interactions decreasing the activation barrier for the hydrogen electro-oxidation reaction

    International Nuclear Information System (INIS)

    Santos, Elizabeth; Schmickler, Wolfgang

    2008-01-01

    A unified model for electrochemical electron transfer reactions which explicitly accounts for the electronic structure of the electrode recently proposed by us is applied to the hydrogen oxidation reaction at different metal electrocatalysts. We focus on the changes produced in the transition state (saddle point) as a consequence of the interactions with d-bands. We discuss different empirical correlations between properties of the metal and catalytic activity proposed in the past. We show which role is played by the band structure of the different metals and its interaction with the molecule for decreasing the activation barrier. Finally, we demonstrate why some metals are better electrocatalysts for the hydrogen electro-oxidation reaction than others

  17. Predictors of decreased physical activity level over time among adults: a longitudinal study.

    Science.gov (United States)

    Dai, Sulan; Wang, Feng; Morrison, Howard

    2014-08-01

    Leisure-time physical activity (LTPA) plays a key role in chronic disease prevention and health promotion. The impact of life-changing events on LTPA among adults is unknown. To examine the association between life-changing events and decreased LTPA levels. Eight cycles of Canadian National Population Health Survey data were used for this study. A total of 12,901 respondents aged ≥18 years in 1994-1995 completed biannual follow-ups until 2008-2009. The association between life-changing events and decreased LTPA in any 2-year period was assessed with adjustment of potential confounding factors. Data were analyzed in 2012. From 1994-1995 to 2008-2009, nine of ten people changed their LTPA levels. Within each 2-year period, individuals were more likely to decrease their LTPA levels if they married within the 2-year period (men); became or remained overweight/obese (women); remained a regular smoker (men); became or remained unhealthy (men and women); developed or continued to have body pain (women); and acquired social support or remained without support (men). Most people change their LTPA levels or patterns, which are significantly influenced by life-changing events. An improved understanding of factors that influence LTPA may help better target those at high risk. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  18. Metavanadate causes cellular accumulation of copper and decreased lysyl oxidase activity

    International Nuclear Information System (INIS)

    Cui, Changtai T.; Uriu-Adams, Janet Y.; Tchaparian, Eskouhie H.; Keen, Carl L.; Rucker, Robert B.

    2004-01-01

    Selected indices of copper metabolism in weanling rats and fibroblast cultures were progressively altered in response to increased levels of sodium metavanadate. In diets, vanadium was added in amounts ranging from 0 to 80 μg V/g of diet, that is, 0-1.6 μmol V/g of diet. In fibroblast cultures, vanadium ranged from 0 to 400 nmol V/ml. The inhibition of P-ATPase-7A activity by metavanadate, important to copper egress from cells, was a primary focus. In skin, and tendon, the copper concentration was increased in response to increased dietary levels of metavanadate, whereas lysyl oxidase activity, a secreted cuproprotein, was reduced. The reduction in lysyl oxidase activity was also accompanied by reduced redox cycling potential of isolated fractions of lysyl oxidase, presumably due to reduced lysyltyrosyl quinone (LTQ) formation at the active site of lysyl oxidase. In contrast, liver copper concentrations and plasma ceruloplasmin activity were not affected by metavanadate exposure. However, semicarbazide-sensitive benzylamine oxidase (SCBO) activity, which was taken as an indirect measure of vascular adhesive protein-1 (VAP-1), was increased. In cultured fibroblasts, cellular copper was also increased and lysyl oxidase decreased in response to metavanadate. Moreover, the steady-state levels of atp7a and lysyl oxidase mRNAs were not affected by addition of metavanadate to culture medium up to 200 nmol/ml. Taken together, these data suggest that pathways involving copper egress and lysyl oxidase activation are particularly sensitive to metavanadate exposure through processes that are predominately posttranslational

  19. Prefrontal activity during response inhibition decreases over time in the postpartum period.

    Science.gov (United States)

    Bannbers, Elin; Gingnell, Malin; Engman, Jonas; Morell, Arvid; Sylvén, Sara; Skalkidou, Alkistis; Kask, Kristiina; Bäckström, Torbjörn; Wikström, Johan; Poromaa, Inger Sundström

    2013-03-15

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    International Nuclear Information System (INIS)

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-01-01

    Research highlights: → Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. → HDAC inhibition decreases Nrf2 protein stability. → HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. → HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H 2 O 2 ) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H 2 O 2 -induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  1. Protein phosphatases decrease their activity during capacitation: a new requirement for this event.

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    Janetti R Signorelli

    Full Text Available There are few reports on the role of protein phosphatases during capacitation. Here, we report on the role of PP2B, PP1, and PP2A during human sperm capacitation. Motile sperm were resuspended in non-capacitating medium (NCM, Tyrode's medium, albumin- and bicarbonate-free or in reconstituted medium (RCM, NCM plus 2.6% albumin/25 mM bicarbonate. The presence of the phosphatases was evaluated by western blotting and the subcellular localization by indirect immunofluorescence. The function of these phosphatases was analyzed by incubating the sperm with specific inhibitors: okadaic acid, I2, endothall, and deltamethrin. Different aliquots were incubated in the following media: 1 NCM; 2 NCM plus inhibitors; 3 RCM; and 4 RCM plus inhibitors. The percent capacitated sperm and phosphatase activities were evaluated using the chlortetracycline assay and a phosphatase assay kit, respectively. The results confirm the presence of PP2B and PP1 in human sperm. We also report the presence of PP2A, specifically, the catalytic subunit and the regulatory subunits PR65 and B. PP2B and PP2A were present in the tail, neck, and postacrosomal region, and PP1 was present in the postacrosomal region, neck, middle, and principal piece of human sperm. Treatment with phosphatase inhibitors rapidly (≤1 min increased the percent of sperm depicting the pattern B, reaching a maximum of ∼40% that was maintained throughout incubation; after 3 h, the percent of capacitated sperm was similar to that of the control. The enzymatic activity of the phosphatases decreased during capacitation without changes in their expression. The pattern of phosphorylation on threonine residues showed a sharp increase upon treatment with the inhibitors. In conclusion, human sperm express PP1, PP2B, and PP2A, and the activity of these phosphatases decreases during capacitation. This decline in phosphatase activities and the subsequent increase in threonine phosphorylation may be an important

  2. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Nicolas [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Thimmulappa, Rajesh [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E. [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Ito, Kazuhiro [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Barnes, Peter J., E-mail: p.j.barnes@imperial.ac.uk [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom)

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  3. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  4. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Science.gov (United States)

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  5. Inhibition of nuclear factor-kappa B activation decreases survival of Mycobacterium tuberculosis in human macrophages.

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    Xiyuan Bai

    Full Text Available Nuclear factor-kappa B (NFκB is a ubiquitous transcription factor that mediates pro-inflammatory responses required for host control of many microbial pathogens; on the other hand, NFκB has been implicated in the pathogenesis of other inflammatory and infectious diseases. Mice with genetic disruption of the p50 subunit of NFκB are more likely to succumb to Mycobacterium tuberculosis (MTB. However, the role of NFκB in host defense in humans is not fully understood. We sought to examine the role of NFκB activation in the immune response of human macrophages to MTB. Targeted pharmacologic inhibition of NFκB activation using BAY 11-7082 (BAY, an inhibitor of IκBα kinase or an adenovirus construct with a dominant-negative IκBα significantly decreased the number of viable intracellular mycobacteria recovered from THP-1 macrophages four and eight days after infection. The results with BAY were confirmed in primary human monocyte-derived macrophages and alveolar macrophages. NFκB inhibition was associated with increased macrophage apoptosis and autophagy, which are well-established killing mechanisms of intracellular MTB. Inhibition of the executioner protease caspase-3 or of the autophagic pathway significantly abrogated the effects of BAY. We conclude that NFκB inhibition decreases viability of intracellular MTB in human macrophages via induction of apoptosis and autophagy.

  6. Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial.

    Science.gov (United States)

    Guillot, Xavier; Tordi, Nicolas; Prati, Clément; Verhoeven, Frank; Pazart, Lionel; Wendling, Daniel

    2017-07-01

    To measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. 30 patients were randomized (ice: 30min, n=15 or cold CO 2 : 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0-3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. The inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: -1 [95% confidence interval: -1.23; -0.77]; ice: -0.73 [-1.06; -0.4]; CO 2 : -0.7 [-1.18; -0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. Local ice and cold CO 2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  7. Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73.

    Science.gov (United States)

    Yang, Xu; Pei, Shimin; Wang, Huanan; Jin, Yipeng; Yu, Fang; Zhou, Bin; Zhang, Hong; Zhang, Di; Lin, Degui

    2017-04-11

    Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5'-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms. We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry. Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate. Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.

  8. Hypoxia decreases creatine uptake in cardiomyocytes, while creatine supplementation enhances HIF activation.

    Science.gov (United States)

    Santacruz, Lucia; Arciniegas, Antonio Jose Luis; Darrabie, Marcus; Mantilla, Jose G; Baron, Rebecca M; Bowles, Dawn E; Mishra, Rajashree; Jacobs, Danny O

    2017-08-01

    Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a specialized creatine transporter (CrT) to maintain intracellular Cr levels. Hypoxia interferes with energy metabolism, including the activity of the creatine energy shuttle, and therefore affects intracellular ATP and PCr levels. Here, we report that exposing cultured cardiomyocytes to low oxygen levels rapidly diminishes Cr transport by decreasing V max and K m Pharmacological activation of AMP-activated kinase (AMPK) abrogated the reduction in Cr transport caused by hypoxia. Cr supplementation increases ATP and PCr content in cardiomyocytes subjected to hypoxia, while also significantly augmenting the cellular adaptive response to hypoxia mediated by HIF-1 activation. Our results indicate that: (1) hypoxia reduces Cr transport in cardiomyocytes in culture, (2) the cytoprotective effects of Cr supplementation are related to enhanced adaptive physiological responses to hypoxia mediated by HIF-1, and (3) Cr supplementation increases the cellular ATP and PCr content in RNCMs exposed to hypoxia. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  9. UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation.

    Science.gov (United States)

    Han, Mira; Ban, Jae-Jun; Bae, Jung-Soo; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-11-14

    The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.

  10. Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

    Science.gov (United States)

    Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

    2018-05-25

    Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

  11. Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

    Science.gov (United States)

    Wu, Fang; Wang, Hong-Yan; Cai, Fan; Wang, Ling-Jie; Zhang, Feng-Ru; Chen, Xiao-Nan; Yang, Qian; Jiang, Meng-Hui; Wang, Xue-Feng; Shen, Wei-Feng

    2015-01-20

    Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.

  12. LECITHIN: CHOLESTEROL ACYLTRANSFERASE ACTIVITY IS DECREASED IN TYPE 2 DIABETES MELLITUS

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    A. Ghanei

    2007-09-01

    Full Text Available Lecithin cholesterol acyltransferase (LCAT plays a major role in the removal of free cholesterol from tissues via assisting HDL-C maturation, and its activity has been proposed as the main indicator of HDL-C function. The aim of the study was to measure LCAT activity in type 2 diabetic patients and to elucidate whether LCAT is associated with metabolic control, and insulin resistance. A case-control study was conducted in Imam Khomeini Hospital during 2006, recruiting 45 type 2 diabetes mellitus patients and 45 healthy subjects. Cases and controls were matched regarding gender, age and body mass index (BMI. FBS, lipid profile, LCAT activity, HbA1C, insulin were measured and insulin resistance (HOMA-IRwas calculated for both patients and controls. The studied variables were then compared between the two groups, and the association of LCAT activity with any of the variables was examined. Twenty-five subjects were female and 20 male both among patients and controls. Mean age of diabetics was 49.9 yrs (range, 40-64, and of controls 51.1 yrs (range, 39-64. FBS, HbA1C, HOMA-IR and TG in patients were significantly higher than controls, and HDL-C in controls was significantly higher than patients. LCAT activity of patients (73 9.1 µmol/L/h was significantly lower than that in controls (88 4.5 µmol/L/h (p<0.001. LCAT activity had significant inverse correlations with HbA1C and duration of diabetes. After multilinear regression analysis in patients, LCAT activity was only correlated with HbA1C level (ß= -0.9, p<0.001. LCAT activity had no significant association with HDL-C and HOMA-IR in any of the groups."nLCAT activity is significantly decreased in patients with type 2 diabetes compared with healthy controls, and has an inverse correlation with the magnitude of hyperglycemia.

  13. College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

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    Julia E. Cohen-Gilbert

    2017-09-01

    Full Text Available The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD multiband functional magnetic resonance imaging (fMRI to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo. Subjects were 23 college freshmen (seven male, 18–20 years who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0. Brain activation on inhibitory trials (NoGo was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations and cluster-based thresholding (z = 2.3, p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC, dorsomedial prefrontal cortex (DMPFC, and anterior cingulate cortex (ACC, brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional

  14. Impaired ALDH2 activity decreases the mitochondrial respiration in H9C2 cardiomyocytes.

    Science.gov (United States)

    Mali, Vishal R; Deshpande, Mandar; Pan, Guodong; Thandavarayan, Rajarajan A; Palaniyandi, Suresh S

    2016-02-01

    Reactive oxygen species (ROS)-mediated reactive aldehydes induce cellular stress. In cardiovascular diseases such as ischemia-reperfusion injury, lipid-peroxidation derived reactive aldehydes such as 4-hydroxy-2-nonenal (4HNE) are known to contribute to the pathogenesis. 4HNE is involved in ROS formation, abnormal calcium handling and more importantly defective mitochondrial respiration. Aldehyde dehydrogenase (ALDH) superfamily contains NAD(P)(+)-dependent isozymes which can detoxify endogenous and exogenous aldehydes into non-toxic carboxylic acids. Therefore we hypothesize that 4HNE afflicts mitochondrial respiration and leads to cell death by impairing ALDH2 activity in cultured H9C2 cardiomyocyte cell lines. H9C2 cardiomyocytes were treated with 25, 50 and 75 μM 4HNE and its vehicle, ethanol as well as 25, 50 and 75 μM disulfiram (DSF), an inhibitor of ALDH2 and its vehicle (DMSO) for 4 h. 4HNE significantly decreased ALDH2 activity, ALDH2 protein levels, mitochondrial respiration and mitochondrial respiratory reserve capacity, and increased 4HNE adduct formation and cell death in cultured H9C2 cardiomyocytes. ALDH2 inhibition by DSF and ALDH2 siRNA attenuated ALDH2 activity besides reducing ALDH2 levels, mitochondrial respiration and mitochondrial respiratory reserve capacity and increased cell death. Our results indicate that ALDH2 impairment can lead to poor mitochondrial respiration and increased cell death in cultured H9C2 cardiomyocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer.

    Science.gov (United States)

    Arsova-Sarafinovska, Zorica; Eken, Ayse; Matevska, Nadica; Erdem, Onur; Sayal, Ahmet; Savaser, Ayhan; Banev, Saso; Petrovski, Daniel; Dzikova, Sonja; Georgiev, Vladimir; Sikole, Aleksandar; Ozgök, Yaşar; Suturkova, Ljubica; Dimovski, Aleksandar J; Aydin, Ahmet

    2009-08-01

    The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO(2)(-)/NO(3)(-)), cGMP and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO(2)(-)/NO(3)(-) and cGMP levels versus controls and BPH groups in both studied samples. This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients.

  16. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chun; Ge, Beihai [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); He, Chao [Department of Cardiology, China Three Gorges University, Yichang 433000 (China); Zhang, Yi; Liu, Xiaowen [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Liu, Kejian [Department of Cardiology, The First Affiliated Hospital of Medical College, Shihezi University (China); Qian, Cuiping; Zhang, Yu; Peng, Wenzhong [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China); Guo, Xiaomei, E-mail: xmguo@tjh.tjmu.edu.cn [Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030 (China)

    2014-07-18

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease.

  17. Mitofusin 2 decreases intracellular lipids in macrophages by regulating peroxisome proliferator-activated receptor-γ

    International Nuclear Information System (INIS)

    Liu, Chun; Ge, Beihai; He, Chao; Zhang, Yi; Liu, Xiaowen; Liu, Kejian; Qian, Cuiping; Zhang, Yu; Peng, Wenzhong; Guo, Xiaomei

    2014-01-01

    Highlights: • Mfn2 decreases cellular lipid accumulation by activating cholesterol transporters. • PPARγ is involved in the Mfn2-mediated increase of cholesterol transporter expressions. • Inactivation of ERK1/2 and p38 is involved in Mfn2-induced PPARγ expression. - Abstract: Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease

  18. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

    Science.gov (United States)

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  19. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    Directory of Open Access Journals (Sweden)

    Laura eFerreri

    2013-11-01

    Full Text Available Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC. 22 healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

  20. Ezetimibe decreased nonalcoholic fatty liver disease activity score but not hepatic steatosis.

    Science.gov (United States)

    Lee, Hyo Young; Jun, Dae Won; Kim, Hyun Jung; Oh, Hyunwoo; Saeed, Waqar Khalid; Ahn, Hyeongsik; Cheung, Ramsey C; Nguyen, Mindie H

    2018-03-20

    A number of clinical trials reported varying effects of cholesterol lowering agents in nonalcoholic fatty liver disease (NAFLD) patients. We, therefore, assessed the changes in hepatic steatosis and NAFLD activity score (NAS) after treatment with cholesterol lowering agents in NAFLD patients by metaanalysis. The Cochrane Library, the MEDLINE, and the Embase databases were searched until May 2015, without any language restrictions, for randomized controlled trials (RCTs) and nonrandomized studies (NRSs). Additional references were obtained from review of bibliography of relevant articles. The quality of evidence was assessed using the grading of recommendations assessment, development and evaluation guidelines. Three RCTs (n = 98) and two NRSs (n = 101) met our study inclusion criteria (adult, NAFLD, liver biopsy). Liver biopsy was performed in all five studies, but only the three studies reported NAS. Ezetimibe significantly decreased NAS (standardized mean difference [SMD], -0.30; 95% confidence interval [CI], -0.57 to -0.03) but not hepatic steatosis in RCT (SMD, -0.1; 95% CI, -0.53 to 0.32), while the effect was significant for both NAS and intrahepatic content in NRSs (SMD, -3.0; 95% CI, -6.9 to 0.91). Ezetimibe decreased NAS without improving hepatic steatosis.

  1. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Directory of Open Access Journals (Sweden)

    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  2. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lugão, A. B.; Varca, G. H.C.; Paiffer, F.; Mathor, M. B.; Lopes, P. S.; Rogero, S.; Rogero, J. R. [Comissão Nacional de Energia Nuclear (CNEN), Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo (Brazil)

    2009-07-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients which were submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through nanoencapsulation with cyclodextrins, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  3. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    International Nuclear Information System (INIS)

    Lugão, A.B.; Varca, G.H.C.; Paiffer, F.; Mathor, M.B.; Lopes, P.S.; Rogero, S.; Rogero, J.R.

    2009-01-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients which were submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through nanoencapsulation with cyclodextrins, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  4. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Lugão, A. B.; Varca, G. H.C.; Mathor, M. B.; Santos Lopes, P.; Rogero, M. S.S.; Rogero, J.R., E-mail: ablugao@ipen.br [Comissão Nacional de Energia Nuclear (CNEN), Instituto de Pesquisas Energeticas e Nucleares (IPEN), Av. Prof. Lineu Prestes, 2242 Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2010-07-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through molecular encapsulation with β-cyclodextrin, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  5. Encapsulation and Nano-Encapsulation of Papain Active Sites to Enhance Radiolityc Stability and Decrease Toxicity

    International Nuclear Information System (INIS)

    Lugão, A.B.; Varca, G.H.C.; Mathor, M.B.; Santos Lopes, P.; Rogero, M.S.S.; Rogero, J.R.

    2010-01-01

    Papain is used as an ingredient in various enzymatic debridement preparations. Those paste-like preparations are based on water solution and usually are sterilized by radiation. As a consequence, there is a major decrease in papain activity. Papain containing preparations are used in chronic wounds treatment in order to clean and remove the necrotic tissue. However FDA (2008) is taking an action against such products due to severe adverse events reported in patients submitted to papain treatments. Thus, the main goal of this proposal is to develop encapsulated papain containing membranes based on hydrogels and silicone rubber in an attempt to achieve a controllable distribution of size and delivery profile, a toxicity reduction and provide stability towards radiation processing through molecular encapsulation with β-cyclodextrin, which may also provide protection to the enzyme against radiation induced radiolysis. (author)

  6. GABAergic inhibition through synergistic astrocytic neuronal interaction transiently decreases vasopressin neuronal activity during hypoosmotic challenge.

    Science.gov (United States)

    Wang, Yu-Feng; Sun, Min-Yu; Hou, Qiuling; Hamilton, Kathryn A

    2013-04-01

    The neuropeptide vasopressin is crucial to mammalian osmotic regulation. Local hypoosmotic challenge transiently decreases and then increases vasopressin secretion. To investigate mechanisms underlying this transient response, we examined the effects of hypoosmotic challenge on the electrical activity of rat hypothalamic supraoptic nucleus (SON) vasopressin neurons using patch-clamp recordings. We found that 5 min exposure of hypothalamic slices to hypoosmotic solution transiently increased inhibitory postsynaptic current (IPSC) frequency and reduced the firing rate of vasopressin neurons. Recovery occurred by 10 min of exposure, even though the osmolality remained low. The γ-aminobutyric acid (GABA)A receptor blocker, gabazine, blocked the IPSCs and the hypoosmotic suppression of firing. The gliotoxin l-aminoadipic acid blocked the increase in IPSC frequency at 5 min and the recovery of firing at 10 min, indicating astrocytic involvement in hypoosmotic modulation of vasopressin neuronal activity. Moreover, β-alanine, an osmolyte of astrocytes and GABA transporter (GAT) inhibitor, blocked the increase in IPSC frequency at 5 min of hypoosmotic challenge. Confocal microscopy of immunostained SON sections revealed that astrocytes and magnocellular neurons both showed positive staining of vesicular GATs (VGAT). Hypoosmotic stimulation in vivo reduced the number of VGAT-expressing neurons, and increased co-localisation and molecular association of VGAT with glial fibrillary acidic protein that increased significantly by 10 min. By 30 min, neuronal VGAT labelling was partially restored, and astrocytic VGAT was relocated to the ventral portion while it decreased in the somatic zone of the SON. Thus, synergistic astrocytic and neuronal GABAergic inhibition could ensure that vasopressin neuron firing is only transiently suppressed under hypoosmotic conditions. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. PPARβ/δ modulates ethanol-induced hepatic effects by decreasing pyridoxal kinase activity

    International Nuclear Information System (INIS)

    Goudarzi, Maryam; Koga, Takayuki; Khozoie, Combiz; Mak, Tytus D.; Kang, Boo-Hyon; Jr, Albert J. Fornace; Peters, Jeffrey M.

    2013-01-01

    Because of the significant morbidity and lethality caused by alcoholic liver disease (ALD), there remains a need to elucidate the regulatory mechanisms that can be targeted to prevent and treat ALD. Toward this goal, minimally invasive biomarker discovery represents an outstanding approach for these purposes. The mechanisms underlying ALD include hepatic lipid accumulation. As the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) has been shown to inhibit steatosis, the present study examined the role of PPARβ/δ in ALD coupling metabolomic, biochemical and molecular biological analyses. Wild-type and Pparβ/δ-null mice were fed either a control or 4% ethanol diet and examined after 4–7 months of treatment. Ethanol fed Pparβ/δ-null mice exhibited steatosis after short-term treatment compared to controls, the latter effect appeared to be due to increased activity of sterol regulatory element binding protein 1c (SREBP1c). The wild-type and Pparβ/δ-null mice fed the control diet showed clear differences in their urinary metabolomic profiles. In particular, metabolites associated with arginine and proline metabolism, and glycerolipid metabolism, were markedly different between genotypes suggesting a constitutive role for PPARβ/δ in the metabolism of these amino acids. Interestingly, urinary excretion of taurine was present in ethanol-fed wild-type mice but markedly lower in similarly treated Pparβ/δ-null mice. Evidence suggests that PPARβ/δ modulates pyridoxal kinase activity by altering K m , consistent with the observed decreased in urinary taurine excretion. These data collectively suggest that PPARβ/δ prevents ethanol-induced hepatic effects by inhibiting hepatic lipogenesis, modulation of amino acid metabolism, and altering pyridoxal kinase activity

  8. Decreased torque and electromyographic activity in the extensor thigh muscles in chondromalacia patellae.

    Science.gov (United States)

    Väätäinen, U; Airaksinen, O; Jaroma, H; Kiviranta, I

    1995-01-01

    The alterations in thigh muscle properties of chondromalacia patellae patients during isometric and dynamic endurance tests were studied using a variokinetic knee testing system linked to surface EMG. A total of 41 patients (chondromalacia group) with arthroscopically certified chondromalacia of the patella were studied. The control group consisted of 31 healthy adult volunteers with no history of knee pain or trauma. Peak torque values were 21% (p chondromalacia group than in the control group. The decrease in the ratio between integrated EMG (IEMG) and measured force were found in all parts of the quadriceps femoris muscle in patients with chondromalacia of the patella in isometric extension. No change in the normalized IEMG levels of the thigh muscles were found between chondromalacia patients and controls in dynamic endurance test. The severity of the chondromalacia of the patella did not affect the level of electromyographic activation in thigh muscles. The ratio of normalized EMG levels of vastus medialis and vastus lateralis did not differ between the groups. The present study showed that chondromalacia patellae patients have reduced force and electromyographic activation levels of quadriceps femoris muscle. Especially, the explosive strength of the quadriceps femoris muscle is reduced.

  9. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    Science.gov (United States)

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-07-01

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Hypoxia-activated prodrug TH-302 decreased survival rate of canine lymphoma cells under hypoxic condition.

    Science.gov (United States)

    Yamazaki, Hiroki; Lai, Yu-Chang; Tateno, Morihiro; Setoguchi, Asuka; Goto-Koshino, Yuko; Endo, Yasuyuki; Nakaichi, Munekazu; Tsujimoto, Hajime; Miura, Naoki

    2017-01-01

    We tested the hypotheses that hypoxic stimulation enhances growth potentials of canine lymphoma cells by activating hypoxia-inducible factor 1α (HIF-1α), and that the hypoxia-activated prodrug (TH-302) inhibits growth potentials in the cells. We investigated how hypoxic culture affects the growth rate, chemoresistance, and invasiveness of canine lymphoma cells and doxorubicin (DOX)-resistant lymphoma cells, and influences of TH-302 on survival rate of the cells under hypoxic conditions. Our results demonstrated that hypoxic culture upregulated the expression of HIF-1α and its target genes, including ATP-binding cassette transporter B1 (ABCB1), ATP-binding cassette transporter G2 (ABCG2), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and survivin, and enhanced the growth rate, DOX resistance, and invasiveness of the cells. Additionally, TH-302 decreased the survival rate of the cells under hypoxic condition. Our studies suggest that hypoxic stimulation may advance the tumorigenicity of canine lymphoma cells, favoring malignant transformation. Therefore, the data presented may contribute to the development of TH-302-based hypoxia-targeting therapies for canine lymphoma.

  11. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors.

    Science.gov (United States)

    Wang, Lei; de Kloet, Annette D; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A; Pioquinto, David J; Ludin, Jacob A; Oh, S Paul; Katovich, Michael J; Frazier, Charles J; Raizada, Mohan K; Krause, Eric G

    2016-06-01

    Over-activation of the brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme 2 (ACE2) inhibits RAS activity by converting angiotensin-II, the effector peptide of RAS, to angiotensin-(1-7), which activates the Mas receptor (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ∼62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the

  12. A pilot of a video game (DDR) to promote physical activity and decrease sedentary screen time.

    Science.gov (United States)

    Maloney, Ann E; Bethea, T Carter; Kelsey, Kristine S; Marks, Julie T; Paez, Sadye; Rosenberg, Angela M; Catellier, Diane J; Hamer, Robert M; Sikich, Linmarie

    2008-09-01

    We examined the feasibility of Dance Dance Revolution (DDR), a dance video game, in participants' homes, to increase physical activity (PA) and to decrease sedentary screen time (SST). Sixty children (7.5 +/- 0.5 years) were randomized in a 2:1 ratio to DDR or to wait-list control (10-week delay). DDR use was logged, PA was measured objectively by accelerometry. SST was self-reported at weeks 0 and 10. At week 28, after both groups had access to DDR, accelerometry and SST were repeated. Mean use of DDR was 89 +/- 82 (range 0-660 min) min per week (mpw). The DDR group showed increased vigorous PA and a reduction in light PA; the control group showed no increase in moderate and/or vigorous PA (MVPA) although they also had a reduction in light PA. Differences between the groups were not observed. The DDR group also reported a decrease in SST of -1.2 +/- 3.7 h per week (hpw) (P increase of +3.0 +/- 7.7 hpw (nonsignificant). The difference in SST between the groups was significant, with less SST in the DDR group. Between weeks 10 and 28, numeric reductions in SST were reported in both groups. In the DDR group, SST at week 28 (8.8 +/- 6.0 hpw) was lower than baseline (10.5 +/- 5.5 hpw; P increases in vigorous PA. Further study is needed to better characterize children and contexts in which DDR may promote a healthy lifestyle.

  13. Construction of Escherichia coli Mutant with Decreased Endotoxic Activity by Modifying Lipid A Structure

    Directory of Open Access Journals (Sweden)

    Qiong Liu

    2015-05-01

    Full Text Available Escherichia coli BL21 (DE3 and its derivatives are widely used for the production of recombinant proteins, but these purified proteins are always contaminated with lipopolysaccharide (LPS. LPS is recognized by the toll-like receptor 4 and myeloid differentiation factor 2 complex of mammalian immune cells and leads to release of pro-inflammatory cytokines. It is a vital step to remove LPS from the proteins before use for therapeutic purpose. In this study, we constructed BL21 (DE3 ∆msbB28 ∆pagP38 mutant, which produces a penta-acylated LPS with reduced endotoxicity. The plasmids harboring pagL and/or lpxE were then introduced into this mutant to further modify the LPS. The new strain (S004 carrying plasmid pQK004 (pagL and lpxE produced mono-phosphoryated tetra-acylated lipid A, which induces markedly less production of tumor necrosis factor-α in the RAW264.7 and IL-12 in the THP1, but still retains ability to produce recombinant proteins. This study provides a strategy to decrease endotoxic activity of recombinant proteins purified from E. coli BL21 backgrounds and a feasible approach to modify lipid A structure for alternative purposes such as mono-phosphoryl lipid A (MPL as vaccine adjuvants.

  14. Decreases in daily physical activity predict acute decline in attention and executive function in heart failure.

    Science.gov (United States)

    Alosco, Michael L; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H; Hayes, Scott M; Josephson, Richard; Hughes, Joel; Gunstad, John

    2015-04-01

    Reduced physical activity (PA) may be one factor that contributes to cognitive decline and dementia in heart failure (HF). Yet, the longitudinal relationship between PA and cognition in HF is poorly understood owing to limitations of past work, including single-time assessments of PA. This is the first study to examine changes in objectively measured PA and cognition over time in HF. At baseline and 12 weeks, 57 HF patients completed psychosocial self-report measures and a neuropsychological battery and wore an accelerometer for 7 days. At baseline, HF patients spent an average of 597.83 (SD 75.91) minutes per day sedentary. Steps per day declined from baseline to the 12-week follow-up; there was also a trend for declines in moderate-vigorous PA. Regression analyses controlling for sex, HF severity, and depressive symptoms showed that decreases in light (P = .08) and moderate-vigorous (P = .04) daily PA emerged as strong predictors of declines in attention/executive function over the 12-week period, but not of memory or language. Reductions in daily PA predicted acute decline in attention/executive function in HF, but not of memory or language. Modifications to daily PA may attenuate cognitive decline, and prospective studies are needed to test this possibility. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Decreased integration and information capacity in stroke measured by whole brain models of resting state activity.

    Science.gov (United States)

    Adhikari, Mohit H; Hacker, Carl D; Siegel, Josh S; Griffa, Alessandra; Hagmann, Patric; Deco, Gustavo; Corbetta, Maurizio

    2017-04-01

    While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to

  16. Decrease of physical activity level in adolescents with limb fractures: an accelerometry-based activity monitor study

    Directory of Open Access Journals (Sweden)

    Delhumeau Cécile

    2011-05-01

    Full Text Available Abstract Background Immobilization and associated periods of inactivity can cause osteopenia, the physiological response of the bone to disuse. Mechanical loading plays an essential role in maintaining bone integrity. Skeletal fractures represent one cause of reduction of the physical activity (PA level in adolescents. The purpose of this study was to quantify the reduction of PA in adolescents with limb fractures during the cast immobilization period compared with healthy controls. Methods Two hundred twenty adolescents were divided into three groups: those with upper limb fractures (50 cases; lower limb fractures (50 cases; and healthy cases (120 cases. Patients and their healthy peers were matched for gender, age, and seasonal assessment of PA. PA level was assessed during cast immobilization by accelerometer. Time spent in PA in each of the different intensity levels - sedentary, light, moderate, and vigorous - was determined for each participant and expressed in minutes and as a percentage of total valid time. Results Reduction in PA during cast immobilization was statistically significant in patients with limb fractures compared to healthy controls. The total PA count (total number of counts/min was significantly lower in those with upper and lower limb fractures (-30.1% and -62.4%, respectively compared with healthy controls (p p = 0.0003 and 76.6% (p p = 0.0008 and 84.4% (p Conclusions PA measured by accelerometer is a useful and valid tool to assess the decrease of PA level in adolescents with limb fractures. As cast immobilization and reduced PA are known to induce bone mineral loss, this study provides important information to quantify the decrease of skeletal loading in this patient population. The observed reduction of high intensity skeletal loading due to the decrease in vigorous PA may explain osteopenia due to disuse, and these data should be kept in mind by trauma practitioners to avoid any unnecessary prolongation of the cast

  17. Type 2 Diabetic Patients with Ischemic Stroke: Decreased Insulin Sensitivity and Decreases in Antioxidant Enzyme Activity Are Related to Different Stroke Subtypes

    Directory of Open Access Journals (Sweden)

    Aleksandra Jotic

    2013-01-01

    C (1.14±0.58, 1.00±0.26 versus 3.14±0.62 min−1/mU/l × 104, P<0.001 and in nondiabetics in D and E versus F (3.38±0.77, 3.03±0.72 versus 6.03±1.69 min−1/mU/l × 104, P<0.001. Also, GSH-Px and GR activities were lower in A and B versus C (GSH-Px: 21.96±3.56,  22.51±1.23 versus 25.12±1.67; GR: 44.37±3.58,  43.50±2.39 versus 48.58±3.67 U/gHb; P<0.001 and in D and E versus F (GSH-Px: 24.75±3.02,  25.57±1.92 versus 28.56±3.91; GR: 48.27±6.81,  49.17±6.24 versus 53.67±3.96 U/gHb; P<0.001. Decreases in Si and GR were significantly related to both ATI and LI in T2D. Our results showed that decreased IS and impaired antioxidant enzymes activity influence ischemic stroke subtypes in T2D. The influence of insulin resistance might be exerted on the level of glutathione-dependent antioxidant enzymes.

  18. Hydrogeochemical surveillance of La Soufriere de Guadeloupe volcano (F. W. I. ), 1979-1985: activity decrease or confining

    Energy Technology Data Exchange (ETDEWEB)

    Bigot, S.; Hammouya, G.

    1987-04-07

    Since the 1975-1977 crisis, changes in physico-chemical characters of La Soufriere's hot springs are observed. These variations have dual origin: - decrease in exchanges between volatile compounds from deep origin and phreatic waters, because of fissures filling by hydrothermal deposits in the whole dome that involves progresive confining: - decrease of volcanic activity.

  19. Decreased salivary sulphotransferase activity correlated with inflammation and autoimmunity parameters in Sjogren's syndrome patients

    DEFF Research Database (Denmark)

    Castro, Isabel; Aguilera, Sergio; Brockhausen, Inka

    2012-01-01

    To determine the expression and enzymatic activities of sulphotransferases involved in mucin hyposulphation in labial salivary glands (LSGs) from SS patients and to correlate sulphotransferase activity with clinical parameters such as secretion, inflammation and serology....

  20. Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments

    Science.gov (United States)

    Kearns, Patrick J.; Angell, John H.; Howard, Evan M.; Deegan, Linda A.; Stanley, Rachel H. R.; Bowen, Jennifer L.

    2016-09-01

    Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy.

  1. GC protein-derived macrophage-activating factor decreases ?-N-acetylgalactosaminidase levels in advanced cancer patients

    OpenAIRE

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo JV; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-01-01

    ?-N-acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort ...

  2. Decreasing Stereotypy in Preschoolers with Autism Spectrum Disorder: The Role of Increased Physical Activity and Function

    Science.gov (United States)

    McLaughlin, Constance Ann Hylton

    2010-01-01

    This study used increased physical activity during recess to reduce stereotypy in preschoolers with Autism Spectrum Disorder. Results indicate increasing physical activity can be used as an intervention to reduce automatically maintained stereotypy in preschoolers with ASD. The intervention had a lesser effect on a preschooler whose stereotypy was…

  3. Effectiveness and feasibility of lowering playground density during recess to promote physical activity and decrease sedentary time at primary school.

    Science.gov (United States)

    D'Haese, Sara; Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Cardon, Greet

    2013-12-10

    This pilot study aimed at investigating the effectiveness of lowering playground density on increasing children's physical activity and decreasing sedentary time. Also the feasibility of this intervention was tested. Data were collected in September and October 2012 in three Belgian schools in 187, 9-12 year old children. During the intervention, playground density was decreased by splitting up recesses and decreasing the number of children sharing the playground. A within-subject design was used. Children wore accelerometers during the study week. Three-level (class - participant - measurement (baseline or intervention)) linear regression models were used to determine intervention effects. After the intervention week the school principals filled out a questionnaire concerning the feasibility of the intervention. The available play space was 12.18 ± 4.19 m²/child at baseline and increased to 24.24 ± 8.51 m²/child during intervention. During the intervention sedentary time decreased (-0.58 min/recess; -3.21%/recess) and moderate-to-vigorous physical activity (+1.04 min/recess; +5.9%/recess) increased during recess and during the entire school day (sedentary time: -3.29%/school day; moderate-to-vigorous physical activity +1.16%/school day). All principals agreed that children enjoyed the intervention; but some difficulties were reported. Lowering playground density can be an effective intervention for decreasing children's sedentary time and increasing their physical activity levels during recess; especially in least active children.

  4. Racemic ketamine decreases muscle sympathetic activity but maintains the neural response to hypotensive challenges in humans

    NARCIS (Netherlands)

    Kienbaum, P.; Heuter, T.; Michel, M. C.; Peters, J.

    2000-01-01

    BACKGROUND: Cardiovascular stimulation and increased catecholamine plasma concentrations during ketamine anesthesia have been attributed to increased central sympathetic activity as well as catecholamine reuptake inhibition in various experimental models. However, direct recordings of efferent

  5. BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE

    Science.gov (United States)

    Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmac...

  6. Oxygen-induced Decrease in the Equilibrium Adsorptive Capacities of Activated Carbons

    OpenAIRE

    Ovín Ania, María Concepción; Parra Soto, José Bernardo; Pis Martínez, José Juan

    2004-01-01

    Special attention was paid in this work to the role of surface chemistry in the adsorption of phenol and salicylic acid onto activated carbons. To this end, two commercial activated carbons (granular and powdered) were oxidised using ammonium peroxodisulphate [(NH4) 2S2O8] and nitric acid in different concentrations. The structural and chemical properties of the oxidised adsorbents were characterised via nitrogen adsorption isotherms measured at –196 ° C and Boehm titrations. Phenol adsorptio...

  7. Andrographolide powder treatment as antifeedant decreased digestive enzyme activity from Plutella xylostella (L.) larvae midgut

    Science.gov (United States)

    Madihah, Malini, Desak Made; Roviani, Hana; Rani, Nessa Vidya; Hermawan, Wawan

    2018-02-01

    Andrographolide, an active compound of Andrographis paniculata, has shown antifeedant activity against Plutella xylostella larvae by disrupting the midgut histological structures. This study aims to determine the activity of andrographolide in crystallized powder form against several digestive enzymes from the midgut of 4th instar P. xylostella larvae. The concentrations used were 0 (control), 1000, 1600, 2500, 4000 and 6500 ppm with four replications each. No-choice antifeedant test with leaf disc method is used in a bioassay for 24 hours. The midgut was dissected from 2nd until 6th segment of 4th instar larvae and was homogenized in iced-buffer solution. Furthermore, larvae's midgut samples were centrifuged at 10,000 rpm, 4°C for 20 min and the supernatant is used as enzyme source. The results showed that andrographolide significantly reduces the amylase, invertase, protease and trypsin activity, as well as total protein concentration compared with control (p<0.05) in a dose-dependent manner. This study provides information about the mode of action of andrographolide in inhibiting feed activity by the reduced digestive enzyme activity of 4th instar P. xylostella larvae.

  8. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Directory of Open Access Journals (Sweden)

    Fang Rao

    Full Text Available Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ. We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg or increased (120, 180, 240 mmHg hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg. The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs. These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  9. PPARγ ligands decrease hydrostatic pressure-induced platelet aggregation and proinflammatory activity.

    Science.gov (United States)

    Rao, Fang; Yang, Ren-Qiang; Chen, Xiao-Shu; Xu, Jin-Song; Fu, Hui-Min; Su, Hai; Wang, Ling

    2014-01-01

    Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ). We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg) or increased (120, 180, 240 mmHg) hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa) binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L) was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg). The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs). These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.

  10. Decreased TK activity alters growth, yield and tolerance to low temperature and low light intensity in transgenic cucumber plants.

    Science.gov (United States)

    Bi, Huangai; Dong, Xubing; Wu, Guoxiu; Wang, Meiling; Ai, Xizhen

    2015-02-01

    Four CsTK antisense transgenic cucumber plants were obtained. Decreased TK activity decreased the photosynthetic rate, seed germination rate, growth yield, and the tolerance to low temperature and weak light stress. Transketolase (TK, EC 2.2.1.1) is a key enzyme in the photosynthetic carbon reduction cycle (Calvin cycle). A cDNA fragment (526 bp) encoding transketolase was cloned from cucumber plants (Cucumis sativa L. cv 'Jinyou 3') by RT-PCR. The antisense expression [(PBI-CsTK(-)] vector containing the CsTK gene fragment was constructed. The resulting plasmid was introduced into the cucumber inbred lines '08-1' using the agrobacterium-mediated method, and four antisense transgenic cucumber plants were obtained. Decreased CsTK expression either unaltered or slightly increased the mRNA abundance and activities of the other main enzymes in the Calvin cycle, however, it decreased the TK activity and net photosynthetic rate (Pn) in antisense transgenic cucumber leaves. Antisense plants showed decreases in the growth, ratio of female flowers and yield compared with the wild-type (WT) plants. The decrease in Pn, stomatal conductance (Gs), transpiration rate (Tr), photochemical efficiency (Fv/Fm) and actual photochemical efficiency of PSII (ΦPSII) and the increase in electrolyte leakage (EL) were greater in antisense transgenic plants than in WT plants under low temperature (5 °C) and low light intensity (100 μmol m(-2) s(-1)).

  11. Odors generated from the Maillard reaction affect autonomic nervous activity and decrease blood pressure through the olfactory system.

    Science.gov (United States)

    Zhou, Lanxi; Ohata, Motoko; Owashi, Chisato; Nagai, Katsuya; Yokoyama, Issei; Arihara, Keizo

    2018-02-01

    Systolic blood pressure (SBP) of rats decreases significantly following exposure to the odor generated from the Maillard reaction of protein digests with xylose. This study identified active odorants that affect blood pressure and demonstrated the mechanism of action. Among the four potent odorants that contribute most to the odor of the Maillard reaction sample, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) and 5-methyl-2-pyrazinemethanol (MPM) decreased SBP significantly. The earliest decrease in blood pressure was observed 5 min after exposure to DMHF. Application of zinc sulfate to the nasal cavity eliminated the effect. Furthermore, gastric vagal (parasympathetic) nerve activity was elevated and renal sympathetic nerve activity was lowered after exposure to DMHF. It is indicated that DMHF affects blood pressure through the olfactory system, and the mechanism for the effect of DMHF on blood pressure involves the autonomic nervous system. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Age-related decrease in physical activity and functional fitness among elderly men and women.

    Science.gov (United States)

    Milanović, Zoran; Pantelić, Saša; Trajković, Nebojša; Sporiš, Goran; Kostić, Radmila; James, Nic

    2013-01-01

    To determine differences in physical activity level and functional fitness between young elderly (60-69 years) and old elderly (70-80 years) people with the hypothesis that an age-related decline would be found. A total of 1288 participants' level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg) and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg). Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test. Significant differences (P men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body-fat percentage, flexibility, agility, and endurance.

  13. Decrease in scale invariance of activity fluctuations with aging and in patients with suprasellar tumors

    DEFF Research Database (Denmark)

    Joustra, S. D.; Gu, C.; Rohling, J. H.T.

    2018-01-01

    -matched healthy controls (age range 21.0–70.6 years). Spontaneous wrist locomotor activity was measured for 7 days with actigraphy, and detrended fluctuation analysis was applied to assess correlations over a range of time scales from minutes to 24 h. For all the subjects, complex scale-invariant correlations...... scale invariance. Conversely, activity patterns at time scales between 10 and 24 h were significantly more regular than all other time scales, and this was mostly associated with age. In conclusion, scale invariance is degraded in healthy subjects at the ages of >33 year as characterized by attenuation......Motor activity in healthy young humans displays intrinsic fluctuations that are scale-invariant over a wide range of time scales (from minutes to hours). Human postmortem and animal lesion studies showed that the intact function of the suprachiasmatic nucleus (SCN) is required to maintain...

  14. Decrease in catalase activity of Folsomia candida fed a Bt rice diet

    DEFF Research Database (Denmark)

    Yuan, Yiyang; Ke, Xin; Chen, Fajun

    2011-01-01

    Here we report the effects of three Bt-rice varieties and their non-Bt conventional isolines on biological traits including survival, reproduction, and the activities of three antioxidant enzymes superoxide dismutase, catalase and peroxidase, in the Collembolan, Folsomia candida. The reproduction...... was significantly lower when fed Kemingdao and Huahui1 than those feeding on their non-GM near-isogenic varieties Xiushui and Minghui63 respectively, this can be explained by the differences of plant compositions depended on variety of rice. The catalase activity of F. candida was significantly lower when fed...

  15. Decreased Oxidative Stress in Male Patients with Active Phase Ankylosing Spondylitis Who Underwent Whole-Body Cryotherapy in Closed Cryochamber

    Directory of Open Access Journals (Sweden)

    Agata Stanek

    2018-01-01

    Full Text Available Objective. The aim of the study was to estimate the impact of whole body cryotherapy (WBC on oxidative stress when performed in a closed cryochamber on patients with ankylosing spondylitis (AS. Material and methods. The effect of ten WBC procedures lasting 3 minutes a day with a subsequent 60-minute session kinesiotherapy on oxidative stress in male AS patients (WBC group n=16 was investigated. To assess the disease activity, the Bath Ankylosing Spondylitis Diseases Activity Index (BASDAI and Bath Ankylosing Spondylitis Functional Index (BASFI were calculated. The WBC group was compared to the kinesiotherapy only (KT; n=16 group. The routine parameters of oxidative stress (antioxidant enzymatic and nonenzymatic antioxidant status, lipid peroxidation products, total oxidative status (TOS, and oxidative stress index (OSI were estimated one day before the beginning and one day after the completion of the research program. Results. After the completion of the treatment in the WBC group, a significant decrease of oxidative stress markers (TOS and OSI and a significant increase of total antioxidant status were observed. The erythrocyte activity of glutathione peroxidase, glutathione reductase decreased significantly in both groups, but the differences of activity of that enzymes prior to post treatment values (Δ in the KT group were significantly higher as compared to the WBC group. The activity of erythrocyte catalase and plasma ZnCu isoenzyme of superoxide dismutase showed a decreased tendency; erythrocyte total superoxide dismutase activity showed an increased tendency in the WBC group after the completion of the treatment. The BASDAI and BASFI decreased significantly in both groups, but the differences of value indexes prior to post treatment (Δ were significantly higher in the WBC than KT group. Conclusion. WBC performed in a closed cryochamber decreases oxidative stress and improves BASDAI and BASFI indexes in male patients during the active

  16. Inhibition of the central melanocortin system decreases brown adipose tissue activity

    NARCIS (Netherlands)

    Kooijman, S.; Boon, M.R.; Parlevliet, E.T.; Geerling, J.J.; Pol, V. van de; Romijn, J.A.; Havekes, L.M.; Meurs, I.; Rensen, P.C.N.

    2014-01-01

    The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose

  17. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  18. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with

  19. Age-related decrease in physical activity and functional fitness among elderly men and women

    Directory of Open Access Journals (Sweden)

    Milanović Z

    2013-05-01

    Full Text Available Zoran Milanovic,1 Saša Pantelic,1 Nebojša Trajkovic,1 Goran Sporiš,2 Radmila Kostic,1 Nic James31Faculty of Sport and Physical Education, University of Niš, Niš, Serbia; 2Faculty of Kinesiology, University of Zagreb, Zagreb, Croatia; 3London Sport Institute, Middlesex University, London, UKAim: To determine differences in physical activity level and functional fitness between young elderly (60–69 years and old elderly (70–80 years people with the hypothesis that an age-related decline would be found.Methods: A total of 1288 participants’ level of physical activity was evaluated using the International Physical Activity Questionnaire: 594 were male (mean ± standard deviation: body height 175.62 ± 9.78 cm; body weight 82.26 ± 31.33 kg and 694 female (mean ± standard deviation: body height 165.17 ± 23.12 cm; body weight 69.74 ± 12.44 kg. Functional fitness was also estimated using the Senior Fitness Test: back scratch, chair sit and reach, 8-foot up and go, chair stand up for 30 seconds, arm curl, and 2-minute step test.Results: Significant differences (P < 0.05 were found for all Senior Fitness tests between young elderly (60–69 years and old elderly (70–80 men. Similar results were found for the women, except no significant differences were found for the chair sit and reach and the 2-minute step test. From the viewpoint of energy consumption estimated by the International Physical Activity Questionnaire, moderate physical activity is dominant. In addition, with aging, among men and women older than 60 years, the value of the Metabolic Equivalent of Task in total physical activity significantly reduces (P < 0.05.Conclusions: This study found that the reduction in physical activity level and functional fitness was equal for both men and women and was due to the aging process. These differences between young and old elderly people were due to the reduction of muscle strength in both upper and lower limbs and changes in body

  20. Increasing physical activity and decreasing sedentary activity in adolescent girls – The Incorporating More Physical Activity and Calcium in Teens (IMPACT study

    Directory of Open Access Journals (Sweden)

    Hergenroeder Albert

    2008-08-01

    .11↓ minutes, 95% CI = 11.74–12.48, p = 0.05 and total daily sedentary activity minutes (mean difference between I and C = 16.99↓ minutes, 95% CI = 16.49–17.50, p = 0.04. Conclusion A well designed and implemented school based health and physical activity intervention can result in a positive influence upon increasing physical activity levels and decreasing sedentary activity. Future interventions should consider a more structured intervention component to obtain significant changes in WBPA.

  1. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

    2007-03-15

    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  2. Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

    OpenAIRE

    Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

    2013-01-01

    Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hy...

  3. Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

    Science.gov (United States)

    Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

    2009-06-10

    Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

  4. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  5. A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G-protein activity and chemoattraction.

    Directory of Open Access Journals (Sweden)

    Thomas J Lampert

    Full Text Available Although G-protein coupled receptors (GPCRs are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490. Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba²⁺ and K⁺, suggesting a decrease in basal excitability (decrease in Ca²⁺ channel activity. The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA and proteose peptone (PP, two known chemoattractants in Tetrahymena. Using microsomal [³⁵S]GTPγS binding assays, we found that wild-type (CU427 have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor, addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein.

  6. Avoidant Responses to Interpersonal Provocation Are Associated with Increased Amygdala and Decreased Mentalizing Network Activity

    Science.gov (United States)

    Krämer, Ulrike M.

    2017-01-01

    When intentionally pushed or insulted, one can either flee from the provoker or retaliate. The implementation of such fight-or-flight decisions is a central aspect in the genesis and evolution of aggression episodes, yet it is usually investigated only indirectly or in nonsocial situations. In the present fMRI study, we aimed to distinguish brain regions associated with aggressive and avoidant responses to interpersonal provocation in humans. Participants (thirty-six healthy young women) could either avoid or face a highly (HP) and a lowly (LP) provoking opponent in a competitive reaction time task: the fight-or-escape (FOE) paradigm. Subjects avoided the HP more often, but retaliated when facing her. Moreover, they chose to fight the HP more quickly, and showed increased heart rate (HR) right before confronting her. Orbitofrontal cortex (OFC) and sensorimotor cortex were more active when participants decided to fight, whereas the mentalizing network was engaged when deciding to avoid. Importantly, avoiding the HP relative to the LP was associated with both higher activation in the right basolateral amygdala and lower relative activity in several mentalizing regions [e.g., medial and inferior frontal gyrus (IFG), temporal-parietal junction (TPJ)]. These results suggest that avoidant responses to provocation might result from heightened threat anticipation and are associated with reduced perspective taking. Furthermore, our study helps to reconcile conflicting findings on the role of the mentalizing network, the amygdala, and the OFC in aggression. PMID:28660251

  7. Using an alternate reality game to increase physical activity and decrease obesity risk of college students.

    Science.gov (United States)

    Johnston, Jeanne D; Massey, Anne P; Marker-Hoffman, Rickie Lee

    2012-07-01

    This quasi-experimental study investigated a game intervention--specifically, an alternate reality game (ARG)--as a means to influence college students' physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story. Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week). A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p students--collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population. © 2012 Diabetes Technology Society.

  8. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

  9. Decreased somatosensory activity to non-threatening touch in combat veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Badura-Brack, Amy S; Becker, Katherine M; McDermott, Timothy J; Ryan, Tara J; Becker, Madelyn M; Hearley, Allison R; Heinrichs-Graham, Elizabeth; Wilson, Tony W

    2015-08-30

    Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder prevalent in combat veterans. Previous neuroimaging studies have demonstrated that patients with PTSD exhibit abnormal responses to non-threatening visual and auditory stimuli, but have not examined somatosensory processing. Thirty male combat veterans, 16 with PTSD and 14 without, completed a tactile stimulation task during a 306-sensor magnetoencephalography (MEG) recording. Significant oscillatory neural responses were imaged using a beamforming approach. Participants also completed clinical assessments of PTSD, combat exposure, and depression. We found that veterans with PTSD exhibited significantly reduced activity during early (0-125 ms) tactile processing compared with combat controls. Specifically, veterans with PTSD had weaker activity in the left postcentral gyrus, left superior parietal area, and right prefrontal cortex in response to nonthreatening tactile stimulation relative to veterans without PTSD. The magnitude of activity in these brain regions was inversely correlated with symptom severity, indicating that those with the most severe PTSD had the most abnormal neural responses. Our findings are consistent with a resource allocation view of perceptual processing in PTSD, which directs attention away from nonthreatening sensory information. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients.

    Science.gov (United States)

    Thyer, Lynda; Ward, Emma; Smith, Rodney; Branca, Jacopo Jv; Morucci, Gabriele; Gulisano, Massimo; Noakes, David; Eslinger, Robert; Pacini, Stefania

    2013-08-01

    α- N -acetylgalactosaminidase (nagalase) accumulates in the serum of cancer patients and its activity correlates with tumor burden, aggressiveness and clinical disease progression. The administration of GC protein-derived macrophage-activating factor (GcMAF) to cancer patients with elevated levels of nagalase has been associated with a decrease of serum nagalase activity and with significant clinical benefits. Here, we report the results of the administration of GcMAF to a heterogeneous cohort of patients with histologically diverse, advanced neoplasms, generally considered as "incurable" diseases. In most cases, GcMAF therapy was initiated at late stages of tumor progression. As this is an open-label, non-controlled, retrospective analysis, caution must be employed when establishing cause-effect relationships between the administration GcMAF and disease outcome. However, the response to GcMAF was generally robust and some trends emerged. All patients (n = 20) presented with elevated serum nagalase activity, well above normal values. All patients but one showed a significant decrease of serum nagalase activity upon weekly GcMAF injections. Decreased nagalase activity was associated with improved clinical conditions and no adverse side effects were reported. The observations reported here confirm and extend previous results and pave the way to further studies aimed at assessing the precise role and indications for GcMAF-based anticancer immunotherapy.

  11. Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

    Science.gov (United States)

    Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

    2015-02-01

    The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

  12. Heavy metal pollution decreases microbial abundance, diversity and activity within particle-size fractions of a paddy soil.

    Science.gov (United States)

    Chen, Junhui; He, Feng; Zhang, Xuhui; Sun, Xuan; Zheng, Jufeng; Zheng, Jinwei

    2014-01-01

    Chemical and microbial characterisations of particle-size fractions (PSFs) from a rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted (NP) soil were performed to investigate whether the distribution of heavy metals (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and diversity at the microenvironment scale. The soils were physically fractionated into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal pollution notably decreased soil basal respiration (a measurement of the total activity of the soil microbial community) and microbial biomass carbon (MBC) across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction was more affected by pollution than the clay fraction and displayed a significantly lower MBC content and respiration and dehydrogenase activity compared with the nonpolluted soils. The abundances and diversities of bacteria were less affected within the PSFs under pollution. However, significant decreases in the abundances and diversities of fungi were noted, which may have strongly contributed to the decrease in MBC. Sequencing of denaturing gradient gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and Chytridiomycota were clearly inhibited under pollution. Our findings suggest that long-term heavy metal pollution decreased the microbial biomass, activity and diversity in PSFs, particularly in the large-size fractions. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  13. Effects of decreased muscle activity on developing axial musculature in nic b107 mutant zebrafish (Danio rerio)

    NARCIS (Netherlands)

    Meulen, van der T.; Schipper, H.; Leeuwen, van J.L.; Kranenbarg, S.

    2005-01-01

    The present paper discusses the effects of decreased muscle activity (DMA) on embryonic development in the zebrafish. Wild-type zebrafish embryos become mobile around 18 h post-fertilisation, long before the axial musculature is fully differentiated. As a model for DMA, the nicb107 mutant was used.

  14. Development of low radio-activated cement. Characteristics of cement and clinker that decreased liquid phase content

    International Nuclear Information System (INIS)

    Ichitsubo, Koki

    2008-01-01

    Low radio-activated cement was developed by decreasing the parent elements of radionuclides in the materials. The characteristics of products, decreasing method of Na, Eu and Co in cement, design, tests, evaluation, and analysis of low radio-activated cement clinker are reported. In order to decrease the content of Na, Eu and Co, the raw materials have to include natural materials such as limestone and silica stone. The production method is the same as white cement. The low radio-activated cement produced by rotary kiln showed 4.9% C 3 A, 1.1% C 4 AF, 26.9% C 3 S and 61.0% C 2 S, which values were standardized by the Japanese Industrial Standards (JIS) of low temperature Portland cement. Another product that decreased a little more liquid phase content showed 4.0% C 3 A, 1.0% C 4 AF, 32.3% C 3 S and 56.5% C 2 S, which was standardized by JIS of sulfate resisting Portland cement. In the case of decommissioning reactor constructed by the low radio-activated cement, the whole amount of waste cement will be no more than the clearance level. (S.Y.)

  15. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang, E-mail: louhongxiang@sdu.edu.cn

    2017-05-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  16. Goatpoxvirus ATPase activity is increased by dsDNA and decreased by zinc ion.

    Science.gov (United States)

    Lee, Ming-Liang; Hsu, Wei-Li; Wang, Chi-Young; Chen, Hui-Yu; Lin, Fong-Yuan; Chang, Ming-Huang; Chang, Hong-You; Wong, Min-Liang; Chan, Kun-Wei

    2016-10-01

    Viral-encoded ATPase can act as a part of molecular motor in genome packaging of DNA viruses, such as vaccinia virus and adenovirus, by ATP hydrolysis and interaction with DNA. Poxviral ATPase (also called A32) is involved in genomic double-stranded DNA (dsDNA) encapsidation, and inhibition of the expression of A32 causes formation of immature virions lacking viral DNA. However, the role of A32 in goatpoxvirus genome packaging and its dsDNA binding property are not known. In this study, purified recombinant goatpoxvirus A32 protein (rA32) was examined for its dsDNA binding property as well as the effect of dsDNA on ATP hydrolysis. We found that rA32 could bind dsDNA, and its ATPase activity was significant increased with dsDNA binding. Effects of magnesium and calcium ions on ATP hydrolysis were investigated also. The ATPase activity was dramatically enhanced by dsDNA in the presence of Mg(2+); in contrast, ATPase function was not altered by Ca(2+). Furthermore, the enzyme activity of rA32 was completely blocked by Zn(2+). Regarding DNA-protein interaction, the rA32-ATP-Mg(2+) showed lower dsDNA binding affinity than that of rA32-ATP-Ca(2+). The DNA-protein binding was stronger in the presence of zinc ion. Our results implied that A32 may play a role in viral genome encapsidation and DNA condensation.

  17. Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels

    International Nuclear Information System (INIS)

    Zhang, Ming; Chang, Wenqiang; Shi, Hongzhuo; Zhou, Yanhui; Zheng, Sha; Li, Ying; Li, Lin; Lou, Hongxiang

    2017-01-01

    Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence. - Highlights: • BD inhibits the filamentation of C. albicans in multiple hypha-inducing conditions. • BD can prolong the survival of nematodes infected by C. albicans. • BD stimulates the expression of Dpp3 to synthesize more farnesol. • BD reduces intracellular cAMP and regulates Ras1-cAMP-PKA pathway.

  18. Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

    KAUST Repository

    Abdel-Azeim, Safwat

    2014-11-11

    Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

  19. Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel-Ab cells.

    Science.gov (United States)

    Kim, Eun-Hyun; Kim, Myo-Kyoung; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2013-10-15

    Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation. © 2013 Elsevier B.V. All rights reserved.

  20. Molecular dynamics characterization of five pathogenic factor X mutants associated with decreased catalytic activity

    KAUST Repository

    Abdel-Azeim, Safwat; Oliva, Romina M.; Chermak, Edrisse; De Cristofaro, Raimondo; Cavallo, Luigi

    2014-01-01

    Factor X (FX) is one of the major players in the blood coagulation cascade. Upon activation to FXa, it converts prothrombin to thrombin, which in turn converts fibrinogen into fibrin (blood clots). FXa deficiency causes hemostasis defects, such as intracranial bleeding, hemathrosis, and gastrointestinal blood loss. Herein, we have analyzed a pool of pathogenic mutations, located in the FXa catalytic domain and directly associated with defects in enzyme catalytic activity. Using chymotrypsinogen numbering, they correspond to D102N, T135M, V160A, G184S, and G197D. Molecular dynamics simulations were performed for 1.68 μs on the wild-type and mutated forms of FXa. Overall, our analysis shows that four of the five mutants considered, D102N, T135M, V160A, and G184S, have rigidities higher than those of the wild type, in terms of both overall protein motion and, specifically, subpocket S4 flexibility, while S1 is rather insensitive to the mutation. This acquired rigidity can clearly impact the substrate recognition of the mutants.

  1. NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

    DEFF Research Database (Denmark)

    Iversen, Marie Beck; Jensen, Simon Kok; Hansen, Anne Louise

    2015-01-01

    . The marine sponge derived lipid αGalCer has recently been demonstrated as a specific agonist for activation of human and murine NKT cells. In the present study we investigated the applicability of αGalCer pre-treatment for immune protection against intra-vaginal HSV-2 infection. We found that C57BL/6 WT mice...... that received local pre-treatment with αGalCer prior to intra-vaginal HSV-2 infection had a lower mean disease score, mortality and viral load in the vagina following infection, compared to mice that did not receive αGalCer pre-treatment. Further, we found increased numbers of CD45 and NK1.1 positive cells...... in vaginal tissue and elevated levels of IFN-γ in the vaginal tissue and in vaginal fluids 24h after αGalCer pre-treatment. Collectively our data demonstrate a protective effect of αGalCer induced activation of NKT cells in the innate immune protection against viral infection....

  2. Decreased physical activity attributable to higher body mass index influences fibromyalgia symptoms.

    Science.gov (United States)

    Vincent, Ann; Clauw, Daniel; Oh, Terry H; Whipple, Mary O; Toussaint, Loren L

    2014-09-01

    Although previous studies report associations between increased body mass index (BMI) and fibromyalgia symptoms, there is uncertainty as to whether this relationship is driven by physical factors, psychological factors, or both. To assess these relationships in a clinical sample of patients with fibromyalgia. Cross-sectional study. Tertiary care facility. A total of 686 patients from an existing national fibromyalgia registry. Patients completed a demographic form and self-report questionnaires including the Fibromyalgia Impact Questionnaire-Revised (FIQ-R), the Medical Outcomes Study Short Form-36 (SF-36), the Brief Pain Inventory (BPI), and the 30-item Profile of Mood States (30-item POMS). FIQ-R overall impact subscale. BMI was significantly correlated with fibromyalgia impact (P BMI and fibromyalgia impact was almost fully accounted for by physical factors and not by psychological factors. Despite patient report that pain hinders physical activity, clinicians who encounter patients with fibromyalgia, particularly patients with increased BMI, should be cognizant of the need to invest time and resources to counsel patients on physical factors (ie, physical activity) that could improve the patients' symptom experience. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  3. RISK DECREASE PROBLEM WITH MAKING ERRORS IN ACTIVITY OF OPERATORS DEALING WITH AUTOMATIC CONTROL SYSTEMS OF GAS-DISTRIBUTION STATIONS

    Directory of Open Access Journals (Sweden)

    V. V. Egorov

    2011-01-01

    Full Text Available The paper contains an analysis of specific features pertaining to the activity of operators dealing with automatic control systems of gas-distribution stations. The professional operator’s activity is presented in the form of the developed data model. Possible conceptual approaches to the research are analyzed in the paper. The paper describes an author’s approach to studying a risk decrease problem in the activity of operators on the basis of the analytical research results. Technology for obtaining  research results is cited in the paper. 

  4. Decrease of GSK3β phosphorylation in the rat nucleus accumbens core enhances cocaine-induced hyper-locomotor activity.

    Science.gov (United States)

    Kim, Wha Y; Jang, Ju K; Lee, Jung W; Jang, Hyunduk; Kim, Jeong-Hoon

    2013-06-01

    Glycogen synthase kinase 3β (GSK3β), which is abundantly present in the brain, is known to contribute to psychomotor stimulant-induced locomotor behaviors. However, most studies have been focused in showing that GSK3β is able to attenuate psychomotor stimulants-induced hyperactivity by increasing its phosphorylation levels in the nucleus accumbens (NAcc). So, here we examined in the opposite direction about the effects of decreased phosphorylation of GSK3β in the NAcc core on both basal and cocaine-induced locomotor activity by a bilateral microinjection into this site of an artificially synthesized peptide, S9 (0.5 or 5.0 μg/μL), which contains sequences around N-terminal serine 9 residue of GSK3β. We found that decreased levels of GSK3β phosphorylation in the NAcc core enhance cocaine-induced hyper-locomotor activity, while leaving basal locomotor activity unchanged. This is the first demonstration, to our knowledge, that the selective decrease of GSK3β phosphorylation levels in the NAcc core may contribute positively to cocaine-induced locomotor activity, while this is not sufficient for the generation of locomotor behavior by itself without cocaine. Taken together, these findings importantly suggest that GSK3β may need other molecular targets which are co-activated (or deactivated) by psychomotor stimulants like cocaine to contribute to generation of locomotor behaviors. © 2013 International Society for Neurochemistry.

  5. Decreased bacteria activity on Si3N4 surfaces compared with PEEK or titanium

    Directory of Open Access Journals (Sweden)

    Puckett S

    2012-09-01

    Full Text Available Deborah Gorth,1 Sabrina Puckett,1 Batur Ercan,1 Thomas J Webster,1 Mohamed Rahaman,2 B Sonny Bal31School of Engineering and Department of Orthopaedics, Brown University, Providence, RI, 2Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO, 3Department of Orthopaedic Surgery, School of Medicine, University of Missouri, Columbia, MO, USAAbstract: A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants – titanium (Ti, poly-ether-ether-ketone (PEEK, and silicon nitride (Si3N4 – were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si3N4 were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si3N4 is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si3N4. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si3N4 were also examined. Significantly greater amounts of these proteins adhered to Si3N4 than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this

  6. HIV-1 transgenic rat CD4+ T cells develop decreased CD28 responsiveness and suboptimal Lck tyrosine dephosphorylation following activation

    International Nuclear Information System (INIS)

    Yadav, Anjana; Pati, Shibani; Nyugen, Anhthu; Barabitskaja, Oxana; Mondal, Prosanta; Anderson, Michael; Gallo, Robert C.; Huso, David L.; Reid, William

    2006-01-01

    Impaired CD4+ T cell responses, resulting in dysregulated T-helper 1 (Th1) effector and memory responses, are a common result of HIV-1 infection. These defects are often preceded by decreased expression and function of the α/β T cell receptor (TCR)-CD3 complex and of co-stimulatory molecules including CD28, resulting in altered T cell proliferation, cytokine secretion and cell survival. We have previously shown that HIV Tg rats have defective development of T cell effector function and generation of specific effector/memory T cell subsets. Here we identify abnormalities in activated HIV-1 Tg rat CD4+ T cells that include decreased pY505 dephosphorylation of Lck (required for Lck activation), decreased CD28 function, reduced expression of the anti-apoptotic molecule Bcl-xL, decreased secretion of the mitogenic lympokine interleukin-2 (IL-2) and increased activation induced apoptosis. These events likely lead to defects in antigen-specific signaling and may help explain the disruption of Th1 responses and the generation of specific effector/memory subsets in transgenic CD4+ T cells

  7. Permafrost thaw and intense thermokarst activity decreases abundance of stream benthic macroinvertebrates.

    Science.gov (United States)

    Chin, Krista S; Lento, Jennifer; Culp, Joseph M; Lacelle, Denis; Kokelj, Steven V

    2016-08-01

    Intensification of permafrost thaw has increased the frequency and magnitude of large permafrost slope disturbances (mega slumps) in glaciated terrain of northwestern Canada. Individual thermokarst disturbances up to 40 ha in area have made large volumes of previously frozen sediments available for leaching and transport to adjacent streams, significantly increasing sediment and solute loads in these systems. To test the effects of this climate-sensitive disturbance regime on the ecology of Arctic streams, we explored the relationship between physical and chemical variables and benthic macroinvertebrate communities in disturbed and undisturbed stream reaches in the Peel Plateau, Northwest Territories, Canada. Highly disturbed and undisturbed stream reaches differed with respect to taxonomic composition and invertebrate abundance. Minimally disturbed reaches were not differentiated by these variables but rather were distributed along a disturbance gradient between highly disturbed and undisturbed sites. In particular, there was evidence of a strong negative relationship between macroinvertebrate abundance and total suspended solids, and a positive relationship between abundance and the distance from the disturbance. Increases in both sediments and nutrients appear to be the proximate cause of community differences in highly disturbed streams. Declines in macroinvertebrate abundance in response to slump activity have implications for the food webs of these systems, potentially leading to negative impacts on higher trophic levels, such as fish. Furthermore, the disturbance impacts on stream health can be expected to intensify as climate change increases the frequency and magnitude of thermokarst. © 2016 John Wiley & Sons Ltd.

  8. Esophageal button battery ingestions: decreasing time to operative intervention by level I trauma activation.

    Science.gov (United States)

    Russell, Robert T; Griffin, Russell L; Weinstein, Elizabeth; Billmire, Deborah F

    2014-09-01

    The incidence of button battery ingestions is increasing and injury due to esophageal impaction begins within minutes of exposure. We changed our management algorithm for suspected button battery ingestions with intent to reduce time to evaluation and operative removal. A retrospective study was performed to identify and evaluate time to treatment and outcome for all esophageal button battery ingestions presenting to a major children's hospital emergency room from February 1, 2010 through February 1, 2012. During the first year, standard emergency room triage (ST) was used. During the second year, the triage protocol was changed and Trauma I triage (TT) was used. 24 children had suspected button battery ingestions with 11 having esophageal impaction. One esophageal impaction was due to 2 stacked coins. Time from arrival in emergency room to battery removal was 183minutes in ST group (n=4) and 33minutes in TT group (n=7) (p=0.04). One patient in ST developed a tracheoesophageal fistula. There were no complications in the TT group. The use of Trauma 1 activations for suspected button battery ingestions has led to more expedient evaluation and shortened time to removal of impacted esophageal batteries. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

    Energy Technology Data Exchange (ETDEWEB)

    Lamparter, Christina L. [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); Winn, Louise M., E-mail: winnl@queensu.ca [Department of Biomedical and Molecular Sciences, Graduate Program in Pharmacology and Toxicology, Queen' s University, Kingston, Ontario K7L 3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L 3N6 (Canada)

    2016-09-01

    The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 h induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity

  10. Overexpression of Nitrate Reductase in Tobacco Delays Drought-Induced Decreases in Nitrate Reductase Activity and mRNA1

    Science.gov (United States)

    Ferrario-Méry, Sylvie; Valadier, Marie-Hélène; Foyer, Christine H.

    1998-01-01

    Transformed (cauliflower mosaic virus 35S promoter [35S]) tobacco (Nicotiana plumbaginifolia L.) plants constitutively expressing nitrate reductase (NR) and untransformed controls were subjected to drought for 5 d. Drought-induced changes in biomass accumulation and photosynthesis were comparable in both lines of plants. After 4 d of water deprivation, a large increase in the ratio of shoot dry weight to fresh weight was observed, together with a decrease in the rate of photosynthetic CO2 assimilation. Foliar sucrose increased in both lines during water stress, but hexoses increased only in leaves from untransformed controls. Foliar NO3− decreased rapidly in both lines and was halved within 2 d of the onset of water deprivation. Total foliar amino acids decreased in leaves of both lines following water deprivation. After 4 d of water deprivation no NR activity could be detected in leaves of untransformed plants, whereas about 50% of the original activity remained in the leaves of the 35S-NR transformants. NR mRNA was much more stable than NR activity. NR mRNA abundance increased in the leaves of the 35S-NR plants and remained constant in controls for the first 3 d of drought. On the 4th d, however, NR mRNA suddenly decreased in both lines. Rehydration at d 3 caused rapid recovery (within 24 h) of 35S-NR transcripts, but no recovery was observed in the controls. The phosphorylation state of the protein was unchanged by long-term drought. There was a strong correlation between maximal extractable NR activity and ambient photosynthesis in both lines. We conclude that drought first causes increased NR protein turnover and then accelerates NR mRNA turnover. Constitutive NR expression temporarily delayed drought-induced losses in NR activity. 35S-NR expression may therefore allow more rapid recovery of N assimilation following short-term water deficit. PMID:9576799

  11. Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.

    Science.gov (United States)

    Reifenberger, Matthew S; Yu, Ling; Bao, Hui-Fang; Duke, Billie Jeanne; Liu, Bing-Chen; Ma, He-Ping; Alli, Ahmed A; Eaton, Douglas C; Alli, Abdel A

    2014-07-01

    Numerous reports have linked cytoskeleton-associated proteins with the regulation of epithelial Na(+) channel (ENaC) activity. The purpose of the present study was to determine the effect of actin cytoskeleton disruption by cytochalasin E on ENaC activity in Xenopus 2F3 cells. Here, we show that cytochalasin E treatment for 60 min can disrupt the integrity of the actin cytoskeleton in cultured Xenopus 2F3 cells. We show using single channel patch-clamp experiments and measurements of short-circuit current that ENaC activity, but not its density, is altered by cytochalasin E-induced disruption of the cytoskeleton. In nontreated cells, 8 of 33 patches (24%) had no measurable ENaC activity, whereas in cytochalasin E-treated cells, 17 of 32 patches (53%) had no activity. Analysis of those patches that did contain ENaC activity showed channel open probability significantly decreased from 0.081 ± 0.01 in nontreated cells to 0.043 ± 0.01 in cells treated with cytochalasin E. Transepithelial current from mpkCCD cells treated with cytochalasin E, cytochalasin D, or latrunculin B for 60 min was decreased compared with vehicle-treated cells. The subcellular expression of fodrin changed significantly, and several protein elements of the cytoskeleton decreased at least twofold after 60 min of cytochalasin E treatment. Cytochalasin E treatment disrupted the association between ENaC and myristoylated alanine-rich C-kinase substrate. The results presented here suggest disruption of the actin cytoskeleton by different compounds can attenuate ENaC activity through a mechanism involving changes in the subcellular expression of fodrin, several elements of the cytoskeleton, and destabilization of the ENaC-myristoylated alanine-rich C-kinase substrate complex. Copyright © 2014 the American Physiological Society.

  12. Radiation-induced progressive decreasing in the expression of reverse transcriptase gene of hEST2 and telomerase activity

    International Nuclear Information System (INIS)

    Zhu Hanneng; Chen Wenying; Xiong Sidong

    2000-01-01

    Telomerase is a ribonucleoprotein complex that adds heximeric repeats called telomeres to the growing ends of chromosomal DNA. Telomerase activity is present in a vast majority of tumors but is repressed in most normal tissues. Human telomerase catalytic subunit gene (hEST2) reverse transcriptase (RT) segment was cloned by PCR according to the sequence published in GeneBank. PCR was used to investigate the expression of the hEST2 RT segment in diverse tumors as well as in various normal tissues. Results indicated that hEST2 RT segment was detectable in tumor cells lines but not in normal cells and tissues. In order to identify the relationship between telomerase and the biological effect of radiation injury, HeLa cells, KB cells and A431 cells were employed to measure the change in telomerase activity after 60 Co-ray irradiation at RNA level and protein level. Quantitative PCR determined that expression of hEST2 RT segment that encodes seven motifs of the human telomeras decreased with increasing dosage of radiation. In addition, a PCR-based telomeric repeat amplification protocol was used to assay telomerase activity after exposure to radiation. The results strongly support the experiments we had made: Telomerase activity decreases with increasing dosage of radiation. We conclude that detection of the hEST2 RT segment by Northern blotting is a new method for detecting telomerase activity. Furthermore, radiation can cause a dose-dependent decrease in telomerase activity. The effect of radiation on telomerase is one possible reason for the death of cancer cells after irradiation. (author)

  13. Decreased material-activation of the complement system using low-energy plasma polymerized poly(vinyl pyrrolidone) coatings

    DEFF Research Database (Denmark)

    Andersen, T.E.; Kolmos, H.J.; Palarasah, Yaseelan

    2011-01-01

    In the current study we investigate the activation of blood complement on medical device silicone rubber and present a plasma polymerized vinyl pyrrolidone (ppVP) coating which strongly decreases surface-activation of the blood complement system. We show that uncoated silicone and polystyrene...... surface. The ppVP surface is furthermore characterized physically and chemically using scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR), which indicates preservation of chemical functionality by the applied plasma process. Overall, the pp...

  14. Using acupressure and Montessori-based activities to decrease agitation for residents with dementia: a cross-over trial.

    Science.gov (United States)

    Lin, Li-Chan; Yang, Man-Hua; Kao, Chieh-Chun; Wu, Shiao-Chi; Tang, Sai-Hung; Lin, Jaung-Geng

    2009-06-01

    To explore the effectiveness of acupressure and Montessori-based activities in decreasing the agitated behaviors of residents with dementia. A double-blinded, randomized (two treatments and one control; three time periods) cross-over design was used. Six special care units for residents with dementia in long-term care facilities in Taiwan were the sites for the study. One hundred thirty-three institutionalized residents with dementia. Subjects were randomized into three treatment sequences: acupressure-presence-Montessori methods, Montessori methods-acupressure-presence and presence-Montessori methods-acupressure. All treatments were done once a day, 6 days per week, for a 4-week period. The Cohen-Mansfield Agitation Inventory, Ease-of-Care, and the Apparent Affect Rating Scale. After receiving the intervention, the acupressure and Montessori-based-activities groups saw a significant decrease in agitated behaviors, aggressive behaviors, and physically nonaggressive behaviors than the presence group. Additionally, the ease-of-care ratings for the acupressure and Montessori-based-activities groups were significantly better than for the presence group. In terms of apparent affect, positive affect in the Montessori-based-activities group was significantly better than in the presence group. This study confirms that a blending of traditional Chinese medicine and a Western activities program would be useful in elderly care and that in-service training for formal caregivers in the use of these interventions would be beneficial for patients

  15. Transgenic overexpression of active calcineurin in beta-cells results in decreased beta-cell mass and hyperglycemia.

    Directory of Open Access Journals (Sweden)

    Ernesto Bernal-Mizrachi

    2010-08-01

    Full Text Available Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+ influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+ signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes.To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP. To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis.Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes.

  16. The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise

    International Nuclear Information System (INIS)

    Shibuya, Kenichi

    2011-01-01

    The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near-infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO 2 and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO 2 : p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task

  17. The effectiveness of workplace interventions to increase physical activity and decrease sedentary behaviour in adults: protocol for a systematic review.

    Science.gov (United States)

    Loitz, Christina C; Potter, Robert J; Walker, Jessica L; McLeod, Nicole C; Johnston, Nora J

    2015-12-12

    A physically active lifestyle plays a preventative role in the development of various chronic diseases and mental health conditions. Unfortunately, few adults achieve the minimum amount of physical activity and spend excessive time sitting. Developing targeted interventions to increase active living among adults is an important endeavour for public health. One plausible context to reach adults is the workplace. This systematic review aims to review the effectiveness of workplace interventions on increasing physical activity and decreasing sedentary behaviour in the workplace. An advisory group of practitioners will work in collaboration with the research team to inform the systematic review and knowledge mobilization. Fifteen electronic databases will be searched to identify studies examining the effectiveness of workplace interventions on physical activity and sedentary behaviour. All experimental designs and observational studies (non-experimental intervention studies) meeting the study criteria will be included. Studies examining generally healthy, employed, adult participants will be included for the review. Interventions will focus on increasing physical activity and/or decreasing sedentary behaviour from the individual to policy level. The primary outcome variables will be reported or observed physical activity and/or sedentary behaviour in the workplace. Secondary outcomes will include variables ranging from return on investment to quality of life. Study quality will be assessed for risk of bias following the protocol identified in the Cochrane Handbook for Systematic Reviews of Interventions and supplemented by the guidelines developed by the Cochrane Effective Practice and Organisation of Care group, using RevMan. The quality of the evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Meta-analyses, forest plots, and harvest plots will be used where appropriate to assess the direction, size, and

  18. Sonographic decreased echogenicity of thyroid parenchyma in asymptomatic population: Correction with thyroid function and thyroid autoimmune activity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji Yeon; Park, Noh Hyuck; Park, Chan Sub; Lee, Ji Ye [Dept. of Radiology, Myongji Hospital, Seonam University College of Medicine, Goyang (Korea, Republic of); Chun, Kyung Ah [Dept. of Radiology, Catholic Kwandong University School of Medicine, Gangneung (Korea, Republic of); Yi, Seong Yoon [Div. of Hematology-Oncology, Dept. of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang (Korea, Republic of); Park, Hee Jin [Dept. of of Radiology, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

    2016-09-15

    The aim of the study was to evaluate the correlation between decreased echogenicity of thyroid and thyroid hormones or autoantibodies. From January 2009 to December 2011, 543 patients with decreased parenchymal echogenicity [M:F = 133:410, median age: 42 years (range: 9-82 years)], who did not have solid nodule, symptom or medication related to thyroid and underwent thyroid function test were retrospectively reviewed. Images were classified based on the degree of hypoechogenicity, heterogenicity or thyroid size. 1) Group A: mild decreased echogenicity, group B: marked decreased echogenicity, 2) group Ho: homogeneous echogenicity, group He: heterogeneous echogenicity, 3) group 1: decreased size, group 2: normal size, group 3: increased size. Differences in triiodiothyronyne (T3), free-thyroxine (fT4), thyrotropin (TSH), anti-thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and anti-TSH receptor antibody (TSH-rAb) were evaluated among groups. T3, fT4, and TSH levels differed between groups A and B (p < 0.001, p = 0.001, p < 0.001). TgAb and TPOAb of group B were higher than group A (p = 0.006, p < 0.001). TPOAb of group He was higher than group Ho (p < 0.001). TSH-rAb and TPOAb of group 3 were higher than group 2 (p = 0.017, p < 0.001). The patients with findings of markedly decreased, heterogeneous echogenicity or thyroid enlargement may have abnormal thyroid function and autoantibodies. These may facilitate the physicians' decision to order tests for thyroid function and autoimmune activity.

  19. Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions.

    Science.gov (United States)

    Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa; Vyavahare, Naren

    2018-04-30

    Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Efficacy of sequential or simultaneous interactive computer-tailored interventions for increasing physical activity and decreasing fat intake.

    Science.gov (United States)

    Vandelanotte, Corneel; De Bourdeaudhuij, Ilse; Sallis, James F; Spittaels, Heleen; Brug, Johannes

    2005-04-01

    Little evidence exists about the effectiveness of "interactive" computer-tailored interventions and about the combined effectiveness of tailored interventions on physical activity and diet. Furthermore, it is unknown whether they should be executed sequentially or simultaneously. The purpose of this study was to examine (a) the effectiveness of interactive computer-tailored interventions for increasing physical activity and decreasing fat intake and (b) which intervening mode, sequential or simultaneous, is most effective in behavior change. Participants (N = 771) were randomly assigned to receive (a) the physical activity and fat intake interventions simultaneously at baseline, (b) the physical activity intervention at baseline and the fat intake intervention 3 months later, (c) the fat intake intervention at baseline and the physical activity intervention 3 months later, or (d) a place in the control group. Six months postbaseline, the results showed that the tailored interventions produced significantly higher physical activity scores, F(2, 573) = 11.4, p physical activity intervention, the simultaneous mode appeared to work better than the sequential mode.

  1. First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding

    International Nuclear Information System (INIS)

    Taulan, M.; Lopez, E.; Guittard, C.; Rene, C.; Baux, D.; Altieri, J.P.; DesGeorges, M.; Claustres, M.; Romey, M.C.

    2007-01-01

    Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter

  2. Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

    Science.gov (United States)

    Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

    2011-08-01

    To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  3. Self-distancing improves interpersonal perceptions and behavior by decreasing medial prefrontal cortex activity during the provision of criticism.

    Science.gov (United States)

    Leitner, Jordan B; Ayduk, Ozlem; Mendoza-Denton, Rodolfo; Magerman, Adam; Amey, Rachel; Kross, Ethan; Forbes, Chad E

    2017-04-01

    Previous research suggests that people show increased self-referential processing when they provide criticism to others, and that this self-referential processing can have negative effects on interpersonal perceptions and behavior. The current research hypothesized that adopting a self-distanced perspective (i.e. thinking about a situation from a non-first person point of view), as compared with a typical self-immersed perspective (i.e. thinking about a situation from a first-person point of view), would reduce self-referential processing during the provision of criticism, and in turn improve interpersonal perceptions and behavior. We tested this hypothesis in an interracial context since research suggests that self-referential processing plays a role in damaging interracial relations. White participants prepared for mentorship from a self-immersed or self-distanced perspective. They then conveyed negative and positive evaluations to a Black mentee while electroencephalogram (EEG) was recorded. Source analysis revealed that priming a self-distanced (vs self-immersed) perspective predicted decreased activity in regions linked to self-referential processing (medial prefrontal cortex; MPFC) when providing negative evaluations. This decreased MPFC activity during negative evaluations, in turn, predicted verbal feedback that was perceived to be more positive, warm and helpful. Results suggest that self-distancing can improve interpersonal perceptions and behavior by decreasing self-referential processing during the provision of criticism. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  4. Piracetam prevents scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities.

    Science.gov (United States)

    Marisco, Patricia C; Carvalho, Fabiano B; Rosa, Michelle M; Girardi, Bruna A; Gutierres, Jessié M; Jaques, Jeandre A S; Salla, Ana P S; Pimentel, Víctor C; Schetinger, Maria Rosa C; Leal, Daniela B R; Mello, Carlos F; Rubin, Maribel A

    2013-08-01

    Piracetam improves cognitive function in animals and in human beings, but its mechanism of action is still not completely known. In the present study, we investigated whether enzymes involved in extracellular adenine nucleotide metabolism, adenosine triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase and adenosine deaminase (ADA) are affected by piracetam in the hippocampus and cerebral cortex of animals subjected to scopolamine-induced memory impairment. Piracetam (0.02 μmol/5 μL, intracerebroventricular, 60 min pre-training) prevented memory impairment induced by scopolamine (1 mg/kg, intraperitoneal, immediately post-training) in the inhibitory avoidance learning and in the object recognition task. Scopolamine reduced the activity of NTPDase in hippocampus (53 % for ATP and 53 % for ADP hydrolysis) and cerebral cortex (28 % for ATP hydrolysis). Scopolamine also decreased the activity of 5'-nucleotidase (43 %) and ADA (91 %) in hippocampus. The same effect was observed in the cerebral cortex for 5'-nucleotidase (38 %) and ADA (68 %) activities. Piracetam fully prevented scopolamine-induced memory impairment and decrease of NTPDase, 5'-nucleotidase and adenosine deaminase activities in synaptosomes from cerebral cortex and hippocampus. In vitro experiments show that piracetam and scopolamine did not alter enzymatic activity in cerebral cortex synaptosomes. Moreover, piracetam prevented scopolamine-induced increase of TBARS levels in hippocampus and cerebral cortex. These results suggest that piracetam-induced improvement of memory is associated with protection against oxidative stress and maintenance of NTPDase, 5'-nucleotidase and ADA activities, and suggest the purinergic system as a putative target of piracetam.

  5. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

    Science.gov (United States)

    van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

    2016-09-01

    Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

  6. Decreased cortical activation in response to a motion stimulus in anisometropic amblyopic eyes using functional magnetic resonance imaging.

    Science.gov (United States)

    Bonhomme, Gabrielle R; Liu, Grant T; Miki, Atsushi; Francis, Ellie; Dobre, M-C; Modestino, Edward J; Aleman, David O; Haselgrove, John C

    2006-12-01

    Motion perception abnormalities and extrastriate abnormalities have been suggested in amblyopia. Functional MRI (fMRI) and motion stimuli were used to study whether interocular differences in activation are detectable in motion-sensitive cortical areas in patients with anisometropic amblyopia. We performed fMRI at 1.5 T 4 control subjects (20/20 OU), 1 with monocular suppression (20/25), and 2 with anisometropic amblyopia (20/60, 20/800). Monocular suppression was thought to be form fruste of amblyopia. The experimental stimulus consisted of expanding and contracting concentric rings, whereas the control condition consisted of stationary concentric rings. Activation was determined by contrasting the 2 conditions for each eye. Significant fMRI activation and comparable right and left eye activation was found in V3a and V5 in all control subjects (Average z-values in L vs R contrast 0.42, 0.43) and in the subject with monocular suppression (z = 0.19). The anisometropes exhibited decreased extrastriate activation in their amblyopic eyes compared with the fellow eyes (zs = 2.12, 2.76). Our data suggest motion-sensitive cortical structures may be less active when anisometropic amblyopic eyes are stimulated with moving rings. These results support the hypothesis that extrastriate cortex is affected in anisometropic amblyopia. Although suggestive of a magnocellular defect, the exact mechanism is unclear.

  7. Increased physical activity not decreased energy intake is associated with inpatient medical treatment for anorexia nervosa in adolescent females.

    Directory of Open Access Journals (Sweden)

    Janine Higgins

    Full Text Available There is a dearth of data regarding changes in dietary intake and physical activity over time that lead to inpatient medical treatment for anorexia nervosa (AN. Without such data, more effective nutritional therapies for patients cannot be devised. This study was undertaken to describe changes in diet and physical activity that precede inpatient medical hospitalization for AN in female adolescents. This data can be used to understand factors contributing to medical instability in AN, and may advance rodent models of AN to investigate novel weight restoration strategies. It was hypothesized that hospitalization for AN would be associated with progressive energy restriction and increased physical activity over time. 20 females, 11-19 years (14.3±1.8 years, with restricting type AN, completed retrospective, self-report questionnaires to assess dietary intake and physical activity over the 6 month period prior to inpatient admission (food frequency questionnaire, Pediatric physical activity recall and 1 week prior (24 hour food recall, modifiable activity questionnaire. Physical activity increased acutely prior to inpatient admission without any change in energy or macronutrient intake. However, there were significant changes in reported micronutrient intake causing inadequate intake of Vitamin A, Vitamin D, and pantothenic acid at 1 week versus high, potentially harmful, intake of Vitamin A over 6 months prior to admission. Subject report of significantly increased physical activity, not decreased energy intake, were associated with medical hospitalization for AN. Physical activity and Vitamin A and D intake should be carefully monitored following initial AN diagnosis, as markers of disease progression as to potentially minimize the risk of medical instability.

  8. Mice heterozygous for the Mdr2 gene demonstrate decreased PEMT activity and diminished steatohepatitis on the MCD diet.

    Science.gov (United States)

    Igolnikov, Alexander C; Green, Richard M

    2006-03-01

    The administration of a methionine and choline deficient (MCD) diet to mice serves as an animal model of NASH. The multidrug resistant 2 (Mdr2) P-glycoprotein encodes for the canalicular phospholipid transporter, and Mdr2 (+/-) mice secrete 40% less phosphatidylcholine than wild-type mice. We have hypothesized that phosphatidylethanolamine-N-methyl transferase (PEMT) up-regulation is a consequence of MCD diet administration, and is important for the pathogenesis of steatohepatitis in this model. However, the effect of decreased phosphatidylcholine secretion and modulation of PEMT on the development of diet-induced steatohepatitis in Mdr2 (+/-) mice has not been explored. Thus, the purpose of the study is to examine the effects of the MCD diet on Mdr2 (+/-) mice. Mdr2 (+/-) and Mdr2 (+/+) mice were treated with an MCD or control diet for up to 30 days, and the severity of steatohepatitis, PEMT activity and hepatic S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) levels were measured. Serum ALT levels, hepatic inflammation, and PEMT activity were significantly lower, and hepatic SAM:SAH ratios were significantly higher in Mdr2 (+/-) mice at 7 and 30 days on the MCD diet. Mdr2 (+/-) mice have diminished susceptibility to MCD diet-induced NASH, which is associated with a relative decrease in PEMT activity and increased SAM:SAH ratios.

  9. Depression-related increases and decreases in appetite reveal dissociable patterns of aberrant activity in reward and interoceptive neurocircuitry

    Science.gov (United States)

    Simmons, W. Kyle; Burrows, Kaiping; Avery, Jason A.; Kerr, Kara L.; Bodurka, Jerzy; Savage, Cary R.; Drevets, Wayne C.

    2016-01-01

    Objective Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites. Method Using functional magnetic resonance imaging we compared brain activity in unmedicated depressed patients with increased or decreased appetite, and healthy control subjects, while viewing photographs of food and non-food objects. We also measured how resting-state functional connectivity related to subjects’ food pleasantness ratings. Results Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings. Conclusions Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body’s physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes. PMID:26806872

  10. Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease.

    Directory of Open Access Journals (Sweden)

    Danillo G Augusto

    Full Text Available The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR=0.49, p=0.003. A strong protective association was found for higher ratios activating/inhibitory KIR (OR=0.44, p=0.001. KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR=0.34, p<10(-3 suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T was decreased in patients. There is evidence that HLA-Bw4(80T may also be important as KIR3DS1 ligand, being the association of this pair (OR=0.07, p=0.001 stronger than KIR3DS1-Bw4(80I (OR=0.31, p=0.002. Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus.

  11. Mean 24-hours sympathetic nervous system activity decreases during head-down tilted bed rest but not during microgravity

    Science.gov (United States)

    Christensen, Nj; Heer, M.; Ivanova, K.; Norsk, P.

    Sympathetic nervous system activity is closely related to gravitational stress in ground based experiments. Thus a high activity is present in the standing-up position and a very low activity is observed during acute head-out water immersion. Adjustments in sympathetic activity are necessary to maintain a constant blood pressure during variations in venous return. Head-down tilted bed rest is applied as a model to simulate changes observed during microgravity. The aim of the present study was to test the hypothesis that mean 24-hours sympathetic activity was low and similar during space flight and in ground based observation obtained during long-term head-down tilted bed rest. Forearm venous plasma noradrenaline was measured by a radioenzymatic technique as an index of muscle sympathetic activity and thrombocyte noradrenaline and adrenaline were measured as indices of mean 24-hours sympathoadrenal activity. Previous results have indicated that thrombocyte noradrenaline level has a half-time of 2 days. Thus to reflect sympathetic activity during a specific experiment the study period must last for at least 6 days and a sample must be obtained within 12 hours after the experiment has ended. Ten normal healthy subjects were studied before and during a 14 days head-down tilted bed rest as well as during an ambulatory study period of a similar length. The whole experiment was repeated while the subjects were on a low calorie diet. Thrombocyte noradrenaline levels were studied in 4 cosmonauts before and within 12 hours after landing after more than 7 days in flight. Thrombocyte noradrenaline decreased markedly during the head-down tilted bed rest (pdifferent in cosmonauts and in subjects participating in the head down tilted bed rest study (170± 29% (Mean± SEM) vs. 57± 7%, respectively; presponse to combined effects of a reduced plasma volume and an increased vascular capacity in flight.

  12. Curcumin modulation of Na,K-ATPase: phosphoenzyme accumulation, decreased K+ occlusion, and inhibition of hydrolytic activity

    DEFF Research Database (Denmark)

    Mahmmoud, Yasser Ahmed

    2005-01-01

    Curcumin, the major constitute of tumeric, is an important nutraceutical that has been shown to be useful in the treatment of many diseases. As an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase, curcumin was shown to correct cystic fibrosis (CF) defects in some model systems, whereas others...... have reported no or little effects on CF after curcumin treatment, suggesting that curcumin effect is not due to simple inhibition of the Ca2+-ATPase. We tested the hypothesis that curcumin may modulate other members of the P2-type ATPase superfamily by studying the effects of curcumin on the activity...... and kinetic properties of the Na,K-ATPase. Curcumin treatment inhibited Na,K-ATPase activity in a dose-dependent manner (K0.514.6 M). Curcumin decreased the apparent affinity of Na,K-ATPase for K+ and increased it for Na+ and ATP. Kinetic analyses indicated that curcumin induces a three-fold reduction...

  13. Thrombotic thrombocytopenic purpura with decreased level of ADAMTS-13 activity and increased level of ADAMTS-13 inhibitor in an adolescent

    Directory of Open Access Journals (Sweden)

    Eun Mi Yang

    2010-03-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

  14. Nonactivated titanium-dioxide nanoparticles promote the growth of Chlamydia trachomatis and decrease the antimicrobial activity of silver nanoparticles.

    Science.gov (United States)

    Bogdanov, A; Janovák, L; Lantos, I; Endrész, V; Sebők, D; Szabó, T; Dékány, I; Deák, J; Rázga, Z; Burián, K; Virok, D P

    2017-11-01

    Chlamydia trachomatis and herpes simplex virus (HSV) are the most prevalent bacterial and viral sexually transmitted infections. Due to the chronic nature of their infections, they are able to interact with titanium-dioxide (TiO 2 ) nanoparticles (NPs) applied as food additives or drug delivery vehicles. The aim of this study was to describe the interactions of these two prevalent pathogens with the TiO 2 NPs. Chlamydia trachomatis and HSV-2 were treated with nonactivated TiO 2 NPs, silver NPs and silver decorated TiO 2 NPs before infection of HeLa and Vero cells. Their intracellular growth was monitored by quantitative PCR. Unexpectedly, the TiO 2 NPs (100 μg ml -1 ) increased the growth of C. trachomatis by approximately fourfold, while the HSV-2 replication was not affected. Addition of TiO 2 to silver NPs decreased their antimicrobial activity against C. trachomatis up to 27·92-fold. In summary, nonactivated TiO 2 NPs could increase the replication of C. trachomatis and decrease the antimicrobial activity of silver NPs. The food industry or drug delivery use of TiO 2 NPs could enhance the growth of certain intracellular pathogens and potentially worsen disease symptoms, a feature that should be further investigated. © 2017 The Society for Applied Microbiology.

  15. Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis.

    Science.gov (United States)

    Lin, Jinpiao; Xiao, Lianbo; Ouyang, Guilin; Shen, Yu; Huo, Rongfen; Zhou, Zhou; Sun, Yue; Zhu, Xianjin; Zhang, Jie; Shen, Baihua; Li, Ningli

    2012-12-01

    Total glucoside of paeony (TGP), an active compound extracted from paeony root, has been used in therapy for rheumatoid arthritis (RA). Th1 and Th17 cells are now believed to play crucial roles in the lesions of RA. However, the molecular mechanism of TGP in inhibition of Th1 and Th17 cells remains unclear. In this study, we found that TGP treatment significantly decreased percentage and number of Th1 and Th17 cells in collagen induced arthritis (CIA) mice. Consistently, treatment with TGP decreased expression of T-bet and RORγt as well as phosphorylation of STAT1 and STAT3. In particular, TGP treatment inhibited dendritic cells (DCs) maturation and reduced production of IL-12 and IL-6. Moreover, TGP-treatment RA patients showed shank population of matured DCs and IFN-γ-, IL-17-producing cells. Taken together, our results demonstrated that TGP inhibited maturation and activation of DCs, which led to impaired Th1 and Th17 differentiation in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Decreased exploratory activity in a mouse model of 15q duplication syndrome; implications for disturbance of serotonin signaling.

    Directory of Open Access Journals (Sweden)

    Kota Tamada

    Full Text Available Autism spectrum disorders (ASDs have garnered significant attention as an important grouping of developmental brain disorders. Recent genomic studies have revealed that inherited or de novo copy number variations (CNVs are significantly involved in the pathophysiology of ASDs. In a previous report from our laboratory, we generated mice with CNVs as a model of ASDs, with a duplicated mouse chromosome 7C that is orthologous to human chromosome 15q11-13. Behavioral analyses revealed paternally duplicated (patDp/+ mice displayed abnormal behaviors resembling the symptoms of ASDs. In the present study, we extended these findings by performing various behavioral tests with C57BL/6J patDp/+ mice, and comprehensively measuring brain monoamine levels with ex vivo high performance liquid chromatography. Compared with wild-type controls, patDp/+ mice exhibited decreased locomotor and exploratory activities in the open field test, Y-maze test, and fear-conditioning test. Furthermore, their decreased activity levels overcame increased appetite induced by 24 hours of food deprivation in the novelty suppressed feeding test. Serotonin levels in several brain regions of adult patDp/+ mice were lower than those of wild-type control, with no concurrent changes in brain levels of dopamine or norepinephrine. Moreover, analysis of monoamines in postnatal developmental stages demonstrated reduced brain levels of serotonin in young patDp/+ mice. These findings suggest that a disrupted brain serotonergic system, especially during postnatal development, may generate the phenotypes of patDp/+ mice.

  17. Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report.

    Science.gov (United States)

    Wang, Dong; Tian, Min; Cui, Guanglin; Wang, Dao Wen

    2018-06-01

    Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in SERPINC1 and PROC lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of PROC and SERPINC1 were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in SERPINC1 and a short deletion variant c.572_574delAGA in PROC. This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the SERPINC1 and PROC gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

  18. Volcanic gas composition changes during the gradual decrease of the gigantic degassing activity of Miyakejima volcano, Japan, 2000-2015

    Science.gov (United States)

    Shinohara, Hiroshi; Geshi, Nobuo; Matsushima, Nobuo; Saito, Genji; Kazahaya, Ryunosuke

    2017-02-01

    The composition of volcanic gases discharged from Miyakejima volcano has been monitored during the intensive degassing activity that began after the eruption in 2000. During the 15 years from 2000 to 2015, Miyakejima volcano discharged 25.5 Mt of SO2, which required degassing of 3 km3 of basaltic magma. The SO2 emission rate peaked at 50 kt/day at the end of 2000 and quickly decreased to 5 kt/day by 2003. During the early degassing period, the volcanic gas composition was constant with the CO2/SO2 = 0.8 (mol ratio), H2O/SO2 = 35, HCl/SO2 = 0.08, and SO2/H2S = 15. The SO2 emission rate decreased gradually to 0.5 kt/day by 2012, and the gas composition also changed gradually to CO2/SO2 = 1.5, H2O/SO2 = 150, HCl/SO2 = 0.15, and SO2/H2S = 6. The compositional changes are not likely caused by changes in degassing pressure or volatile heterogeneity of a magma chamber but are likely attributed to an increase of hydrothermal scrubbing caused by large decrease of the volcanic gas emission rate, suggesting a supply of gases with constant composition during the 15 years. The intensive degassing was modeled based on degassing of a convecting magma conduit. The gradual SO2 emission rate that decrease without changes in volcanic gas composition is attributed to a reduction of diameter of the convecting magma conduit.

  19. Activation of PPARα decreases bile acids in livers of female mice while maintaining bile flow and biliary bile acid excretion.

    Science.gov (United States)

    Zhang, Youcai; Lickteig, Andrew J; Csanaky, Iván L; Klaassen, Curtis D

    2018-01-01

    Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver. In contrast, WT female mice were less susceptible to these CLOF-mediated responses observed in males. In WT female mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs of hepatic BA-related genes. Next, a comparative analysis between WT and PPARα-null female mice showed that lack of PPARα in female mice decreased total BAs in serum, but had little effect on total BAs in liver or bile. However, lack of PPARα in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3). Furthermore, the increase of Cyp7a1 in PPARα-null female mice was associated with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are resistant to CLOF-mediated effects on BA metabolism observed in males, which could be attributed to PPARα-mediated suppression in females on genes involved in BA synthesis and transport. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

    Science.gov (United States)

    Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

    2018-01-01

    : Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

  1. Decrease in fMRI brain activation during working memory performed after sleeping under 10 lux light.

    Science.gov (United States)

    Kang, Seung-Gul; Yoon, Ho-Kyoung; Cho, Chul-Hyun; Kwon, Soonwook; Kang, June; Park, Young-Min; Lee, Eunil; Kim, Leen; Lee, Heon-Jeong

    2016-11-09

    The aim of this study was to investigate the effect of exposure to dim light at night (dLAN) when sleeping on functional brain activation during a working-memory tasks. We conducted the brain functional magnetic resonance imaging (fMRI) analysis on 20 healthy male subjects. All participants slept in a polysomnography laboratory without light exposure on the first and second nights and under a dim-light condition of either 5 or 10 lux on the third night. The fMRI scanning was conducted during n-back tasks after second and third nights. Statistical parametric maps revealed less activation in the right inferior frontal gyrus (IFG) after exposure to 10-lux light. The brain activity in the right and left IFG areas decreased more during the 2-back task than during the 1- or 0-back task in the 10-lux group. The exposure to 5-lux light had no significant effect on brain activities. The exposure to dLAN might influence the brain function which is related to the cognition.

  2. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  3. Blockade of NMDA receptors decreased spinal microglia activation in bee venom induced acute inflammatory pain in rats.

    Science.gov (United States)

    Li, Li; Wu, Yongfang; Bai, Zhifeng; Hu, Yuyan; Li, Wenbin

    2017-03-01

    Microglial cells in spinal dorsal horn can be activated by nociceptive stimuli and the activated microglial cells release various cytokines enhancing the nociceptive transmission. However, the mechanisms underlying the activation of spinal microglia during nociceptive stimuli have not been well understood. In order to define the role of NMDA receptors in the activation of spinal microglia during nociceptive stimuli, the present study was undertaken to investigate the effect of blockade of NMDA receptors on the spinal microglial activation induced by acute peripheral inflammatory pain in rats. The acute inflammatory pain was induced by subcutaneous bee venom injection to the plantar surface of hind paw of rats. Spontaneous pain behavior, thermal withdrawal latency and mechanical withdrawal threshold were rated. The expression of specific microglia marker CD11b/c was assayed by immunohistochemistry and western blot. After bee venom treatment, it was found that rats produced a monophasic nociception characterized by constantly lifting and licking the injected hind paws, decreased thermal withdrawal latency and mechanical withdrawal threshold; immunohistochemistry displayed microglia with enlarged cell bodies, thickened, extended cellular processes with few ramifications, small spines, and intensive immunostaining; western blot showed upregulated expression level of CD11b/c within the period of hyperalgesia. Prior intrathecal injection of MK-801, a selective antagonist of NMDA receptors, attenuated the pain behaviors and suppressed up-regulation of CD11b/c induced by bee venom. It can be concluded that NMDA receptors take part in the mediation of spinal microglia activation in bee venom induced peripheral inflammatory pain and hyperalgesia in rats.

  4. Memantine Can Reduce Ethanol-Induced Caspase-3 Activity and Apoptosis in H4 Cells by Decreasing Intracellular Calcium.

    Science.gov (United States)

    Wang, Xiaolong; Chen, Jiajun; Wang, Hongbo; Yu, Hao; Wang, Changliang; You, Jiabin; Wang, Pengfei; Feng, Chunmei; Xu, Guohui; Wu, Xu; Zhao, Rui; Zhang, Guohua

    2017-08-01

    Caspase-3 activation and apoptosis are associated with various neurodegenerative disorders. Calcium activation is an important factor in promoting apoptosis. We, therefore, assessed the role of intracellular calcium in ethanol-induced activation of caspase-3 in H4 human neuroglioma cells and the protective effect of the NMDA receptor antagonist, memantine, on ethanol-induced apoptosis in H4 cells. H4 cells were treated with 100 mM EtOH (in culture medium) for 2 days. For interaction studies, cells were treated with memantine (4 μM), EDTA (1 mM), or BAPTA-AM (10 μM) before treatment with EtOH. Knockdown of the gene encoding the NR1 subunit of the NMDA receptor was performed using RNAi. Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry. Cell viability was detected using an MTS cell proliferation kit. Fluorescence dual wavelength spectrophotometry was used to determine the intracellular calcium concentration. The levels of NR1, caspase-3, IP3R1, and SERCA1 proteins were detected by western blotting. NR1, IP3R1, and SERCA1 mRNA levels were detected by qPCR. We observed increased expression of NR1, IP3R1, SERCA1, and increased intracellular levels of calcium ions in H4 cells exposed to ethanol. In addition, the calcium chelators, EDTA and BAPTA, and RNAi disruption of the NMDA receptor reduced ethanol-induced caspase-3 activation in H4 cells. Memantine treatment reduced the ethanol-induced increase of intracellular calcium, caspase-3 activation, apoptosis, and the ethanol-induced decrease in cell viability. Our results indicate that ethanol-induced caspase-3 activation and apoptosis are likely to be dependent on cytosolic calcium levels and that they can be reduced by memantine treatment.

  5. ESTIMATION OF DECREASING LOSSES OF ACTIVE POWER IN TRANSFORMERS IN SETTING BATTERY OF LOW-VOLTAGE CAPACITORS

    Directory of Open Access Journals (Sweden)

    V. N. Radkevich

    2014-01-01

    Full Text Available This paper describes an estimation method of decreasing losses of active power in power transformers with voltage 10(6/0,4 kV after installation of devices of reactive power compensation on output side depending on voltage level, connected to capacity devices, taking into account dielectric loss in capacitors. Analysis of functional dependences was carried out. Investigation of function with a help of derivations was carried out. Points of function extremum and also its intervals of rise and fall rates were founded. This paper describes graphic investigation of obtained functional dependence, which is introduced by quartic polynominal. It is established that decreasing of losses of active power depends on technical parameters and load factor of transformer, coefficient of loading power of electricity consumers, voltage value connected to capacitor unit.Using obtained functional dependences, calculations for the main size-types of power transformers with voltage 10(6/0,4 kV serie ТМГ 11 and ТМГ12 were done. It is established that depending on technical characteristics of certain transformer, coefficient of its loading and power, there is a definite value of deviation of real voltage value from working voltage of capacitor installation when it will be observed positive technical and economical effect from installed capacitor battery unit. For taken value of loading coefficient and transformer’s power the maximum decrease of losses of active power takes place under voltage directed to capacitor unit, which is lower then nominal value. For all taken size-types of power transformers the argument of investigating function for its maximal value is out of standard permissible of voltage deviations from nominal value.These functional dependents can be used for preliminary calculations, which are needed for making decision on compensation of reactive power in electric power supply systems of industrial objects. Their consideration allows more

  6. Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats.

    Science.gov (United States)

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H; Tang, Jiping

    2010-02-15

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals.

  7. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    Science.gov (United States)

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  8. Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.

    Science.gov (United States)

    Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena; Wozniak, Michal

    2017-06-01

    Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

    Science.gov (United States)

    Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

    2016-01-01

    To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

  10. Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-α

    Science.gov (United States)

    Huang, Xian-sheng; Zhao, Shui-ping; Bai, Lin; Hu, Min; Zhao, Wang; Zhang, Qian

    2009-01-01

    Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferator-activated receptor-α (PPARα) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARα was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARα (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications: A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARα. PMID:19694729

  11. Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

    Science.gov (United States)

    Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M

    2017-10-11

    Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

  12. Higher energy intake at dinner decreases parasympathetic activity during nighttime sleep in menstruating women: A randomized controlled trial.

    Science.gov (United States)

    Tada, Yuki; Yoshizaki, Takahiro; Tanaka, Izumi; Kanehara, Rieko; Kato, Misao; Hatta, Naoko; Hida, Azumi; Kawano, Yukari

    2018-06-09

    Previous studies have found more frequent increases in dietary intake and nonrestorative nocturnal sleep during the luteal phase than in the follicular phase, but few studies have investigated how increased energy intake at dinner influences sleep by considering the correlation between female hormone and cardiac autonomic nervous system (ANS) activity. This study examined the effects of energy intake at dinner on ANS activity during nighttime sleep in order to evaluate restorative sleep in healthy women. We also examined whether ANS activity is associated with female hormone dynamics. Twenty-four healthy collegiate women participated in this randomized crossover trial. Each was assigned to receive a High Energy Dinner (HED) or Low Energy Dinner (LED) treatment. Energy ratios of each test meal (breakfast, lunch, and dinner) to total energy intake were 1:1:2 and 1:2:1 for HED and LED treatments, respectively. Each participant wore an ECG recorder before dinner and removed it upon waking the next morning. Power spectral analysis of heart rate variability was used to calculate low frequency (LF), high frequency (HF), and total spectral power (TP). Cardiac sympathetic (SNS) and parasympathetic (PNS) nervous system activity were evaluated as LF/HF and HF/TP, respectively. Mean HF/TP for the entire sleeping period was lower with HED treatment compared to LED treatment (41.7 ± 11.4 vs. 45.0 ± 12.13, P = .034). Intergroup comparisons of the initial 3-h sleeping period revealed that LF/HF (0.87 ± 0.82 vs. 0.66 ± 0.82, P = .013) and HF/TP (45.6 ± 13.9 vs. 51.5 ± 11.8, P = .002) were higher and lower, respectively, with HED treatment compared to LED treatment. Progesterone levels were positively correlated with LF/HF with LED treatment, and negatively correlated with HF/TP with both HED and LED treatments. Higher energy intake at dinner increases and decreases SNS and PNS activities, respectively, resulting in nonrestorative nocturnal

  13. [CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

    Science.gov (United States)

    Sizonov, V A; Dmitrieva, L E; Kuznetsov, S V

    2015-01-01

    Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

  14. NS309 decreases rat detrusor smooth muscle membrane potential and phasic contractions by activating SK3 channels

    Science.gov (United States)

    Parajuli, Shankar P; Hristov, Kiril L; Soder, Rupal P; Kellett, Whitney F; Petkov, Georgi V

    2013-01-01

    Background and Purpose Overactive bladder (OAB) is often associated with abnormally increased detrusor smooth muscle (DSM) contractions. We used NS309, a selective and potent opener of the small or intermediate conductance Ca2+-activated K+ (SK or IK, respectively) channels, to evaluate how SK/IK channel activation modulates DSM function. Experimental Approach We employed single-cell RT-PCR, immunocytochemistry, whole cell patch-clamp in freshly isolated rat DSM cells and isometric tension recordings of isolated DSM strips to explore how the pharmacological activation of SK/IK channels with NS309 modulates DSM function. Key Results We detected SK3 but not SK1, SK2 or IK channels expression at both mRNA and protein levels by RT-PCR and immunocytochemistry in DSM single cells. NS309 (10 μM) significantly increased the whole cell SK currents and hyperpolarized DSM cell resting membrane potential. The NS309 hyperpolarizing effect was blocked by apamin, a selective SK channel inhibitor. NS309 inhibited the spontaneous phasic contraction amplitude, force, frequency, duration and tone of isolated DSM strips in a concentration-dependent manner. The inhibitory effect of NS309 on spontaneous phasic contractions was blocked by apamin but not by TRAM-34, indicating no functional role of the IK channels in rat DSM. NS309 also significantly inhibited the pharmacologically and electrical field stimulation-induced DSM contractions. Conclusions and Implications Our data reveal that SK3 channel is the main SK/IK subtype in rat DSM. Pharmacological activation of SK3 channels with NS309 decreases rat DSM cell excitability and contractility, suggesting that SK3 channels might be potential therapeutic targets to control OAB associated with detrusor overactivity. PMID:23145946

  15. Amelioration of radiation induced decrease in activity of catalase and superoxide dismutase in mouse liver by Punica granatum

    International Nuclear Information System (INIS)

    Sharma, Jaimala; Mathur, Aarti

    2013-01-01

    Ionizing radiation generates reactive oxygen species (ROS) in irradiated tissue. Cells of liver have their own defence system, the antioxidant system to deactivate ROS. Antioxidant system includes enzymatic and non-enzymatic components. Liver is rich in endogenous antioxidants and related enzymes. Catalase and Superoxide dismutase (SOD) are powerful antioxidant enzymes. In the present study Punica granatum fruit rind Ethanol extract (PGFRE) was tested against 60 Co gamma radiation induced alteration in Swiss albino mouse. Healthy adult (25±2) Swiss albino mouse were selected and divided into four groups. The first group was sham irradiated. The second group was irradiated with 8 Gy 60 Co gamma radiation only and served as control. The third group was administered with Ethanol extract of Punica granatum fruit rind one hour before irradiation at the dose rate of 10 mg/kg body weight orally. Animals were exposed to 8 Gy 60 Co gamma radiation. Fourth group was administered with Ethanol extract of Punica granatum fruit rind at the dose rate of 10 mg/kg body weight. Mice were sacrificed at various post irradiation intervals and liver was removed, weighed and analysed biochemically for Catalase and SOD activity. Catalase and SOD activity decreased up till 7th post irradiation day in 8 Gy irradiated group than normal. In PGFRE pretreated irradiated group catalase and SOD activity were higher than the corresponding control group at all the intervals. These results indicate that PGFRE extract protects damage to the catalase and SOD activity in liver of Swiss albino mouse against lethal dose of gamma radiation. (author)

  16. Stimulation of the ventral tegmental area increased nociceptive thresholds and decreased spinal dorsal horn neuronal activity in rat.

    Science.gov (United States)

    Li, Ai-Ling; Sibi, Jiny E; Yang, Xiaofei; Chiao, Jung-Chih; Peng, Yuan Bo

    2016-06-01

    Deep brain stimulation has been found to be effective in relieving intractable pain. The ventral tegmental area (VTA) plays a role not only in the reward process, but also in the modulation of nociception. Lesions of VTA result in increased pain thresholds and exacerbate pain in several pain models. It is hypothesized that direct activation of VTA will reduce pain experience. In this study, we investigated the effect of direct electrical stimulation of the VTA on mechanical, thermal and carrageenan-induced chemical nociceptive thresholds in Sprague-Dawley rats using our custom-designed wireless stimulator. We found that: (1) VTA stimulation itself did not show any change in mechanical or thermal threshold; and (2) the decreased mechanical and thermal thresholds induced by carrageenan injection in the hind paw contralateral to the stimulation site were significantly reversed by VTA stimulation. To further explore the underlying mechanism of VTA stimulation-induced analgesia, spinal cord dorsal horn neuronal responses to graded mechanical stimuli were recorded. VTA stimulation significantly inhibited dorsal horn neuronal activity in response to pressure and pinch from the paw, but not brush. This indicated that VTA stimulation may have exerted its analgesic effect via descending modulatory pain pathways, possibly through its connections with brain stem structures and cerebral cortex areas.

  17. Early decrease in total hemolytic complement activity (CH100) after fasting or intestinal bypass in the rat.

    Science.gov (United States)

    Montanari, M; Violi, V; Muri, M; Roncoroni, L; Mora, G; Ronzoni, M

    1986-01-01

    An evaluation of total hemolytic complement activity (CH100) after fasting or intestinal bypass was performed in rats. The experiment lasted 6 days. Three groups, of 5 animals each, were studied. On the 1st day, basal values of total complement (TC), albumin and body weight were determined. Group A received normal, ad libitum feeding, group B started on a 'water only' diet, group C underwent intestinal bypass. On the 4th and 6th day the parameters were assessed. TC mean values were significantly lower in groups B and C, as compared to group A, on the 4th as well as on the 6th day (p less than 0.01 by Mann-Whitney's U test). Body weight showed a similar trend. Differences in albumin were never statistically significant. Limitations of the analytical method are discussed. The data show that fasting or bypass-induced malabsorption may determine an early decrease in total hemolytic complement activity, though a development of an immune deficiency is not proved.

  18. The Natural Stilbenoid Piceatannol Decreases Activity and Accelerates Apoptosis of Human Neutrophils: Involvement of Protein Kinase C

    Directory of Open Access Journals (Sweden)

    Viera Jancinova

    2013-01-01

    Full Text Available Neutrophils are able to release cytotoxic substances and inflammatory mediators, which, along with their delayed apoptosis, have a potential to maintain permanent inflammation. Therefore, treatment of diseases associated with chronic inflammation should be focused on neutrophils; formation of reactive oxygen species and apoptosis of these cells represent two promising targets for pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has the ability to reduce the toxic action of neutrophils. This substance decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. Radicals formed within neutrophils (fulfilling a regulatory role were reduced to a lesser extent than extracellular oxidants, potentially dangerous for host tissues. Moreover, piceatannol did not affect the phosphorylation of p40phox—a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular (granular membranes. The stilbenoid tested elevated the percentage of early apoptotic neutrophils, inhibited the activity of protein kinase C (PKC—the main regulatory enzyme in neutrophils, and reduced phosphorylation of PKC isoforms α, βII, and δ on their catalytic region. The results indicated that piceatannol may be useful as a complementary medicine in states associated with persisting neutrophil activation and with oxidative damage of tissues.

  19. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, Nicole M., E-mail: nicolegardner@creighton.edu [Department of Pharmacology, Creighton University School of Medicine, Omaha, NE 68178 (United States); Riley, Ronald T.; Showker, Jency L.; Voss, Kenneth A. [USDA-ARS, Toxicology and Mycotoxin Research Unit, Athens, GA 30605 (United States); Sachs, Andrew J.; Maddox, Joyce R.; Gelineau-van Waes, Janee B. [Department of Pharmacology, Creighton University School of Medicine, Omaha, NE 68178 (United States)

    2016-05-01

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. - Highlights: • FB1 treatment results in accumulation of Sa1P primarily in the nucleus of MEFs. • FB1 treatment and elevated nuclear Sa1P are associated with HDAC inhibition. • Sphk2 inhibition alone

  20. Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Gardner, Nicole M.; Riley, Ronald T.; Showker, Jency L.; Voss, Kenneth A.; Sachs, Andrew J.; Maddox, Joyce R.; Gelineau-van Waes, Janee B.

    2016-01-01

    Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in the nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. - Highlights: • FB1 treatment results in accumulation of Sa1P primarily in the nucleus of MEFs. • FB1 treatment and elevated nuclear Sa1P are associated with HDAC inhibition. • Sphk2 inhibition alone

  1. Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells

    International Nuclear Information System (INIS)

    Miyata, Yoshiki; Sato, Takashi; Ito, Akira

    2005-01-01

    Triptolide, a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook f., exerts antitumorigenic actions against several tumor cells, but the intracellular target signal molecule(s) for this antitumorigenesis activity of triptolide remains to be identified. In the present study, we demonstrated that triptolide, in a dose-dependent manner, inhibited the proliferation of human fibrosarcoma HT-1080, human squamous carcinoma SAS, and human uterine cervical carcinoma SKG-II cells. In addition, triptolide was found to decrease phosphatidylinositol 3-kinase (PI3K) activity. A PI3K inhibitor, LY-294002, mimicked the triptolide-induced antiproliferative activity in HT-1080, SAS, and SKG-II cells. There was no change in the activity of Akt or protein kinase C (PKC), both of which are downstream effectors in the PI3K pathway. Furthermore, the phosphorylation of Ras, Raf, and mitogen-activated protein/extracellular signal-regulated kinase 1/2 was not modified in HT-1080 cells treated with triptolide. However, the phosphorylation of c-Jun NH 2 -terminal kinase 1 (JNK1) was found to increase in both triptolide- and LY-294002-treated cells. Furthermore, the triptolide-induced inhibition of HT-1080 cell proliferation was not observed by JNK1 siRNA-treatment. These results provide novel evidence that PI3K is a crucial target molecule in the antitumorigenic action of triptolide. They further suggest a possible triptolide-induced inhibitory signal for tumor cell proliferation that is initiated by the decrease in PI3K activity, which in turn leads to the augmentation of JNK1 phosphorylation via the Akt and/or PKC-independent pathway(s). Moreover, it is likely that the activation of JNK1 is required for the triptolide-induced inhibition of tumor proliferation

  2. Appetite - decreased

    Science.gov (United States)

    Loss of appetite; Decreased appetite; Anorexia ... Any illness can reduce appetite. If the illness is treatable, the appetite should return when the condition is cured. Loss of appetite can cause weight ...

  3. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid

    Directory of Open Access Journals (Sweden)

    Liu X

    2014-02-01

    Full Text Available Xudong Liu,1,* Yuchao Zhang,1,* Jinquan Li,1 Dong Wang,1 Yang Wu,1 Yan Li,2 Zhisong Lu,3 Samuel CT Yu,4 Rui Li,1 Xu Yang1 1Laboratory of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, People's Republic of China; 2Chemical and Biomolecular Engineering Department, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region; 3Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing, People's Republic of China; 4Division of Environment, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region *These authors contributed equally to this work Abstract: Single-walled carbon nanotubes (SWCNTs have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test, brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH], inflammation (nuclear factor κB, tumor necrosis factor a, interleukin-1β, and apoptosis (cysteine-aspartic acid protease 3 in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of

  4. A quality improvement project sustainably decreased time to onset of active physical therapy intervention in patients with acute lung injury.

    Science.gov (United States)

    Dinglas, Victor D; Parker, Ann M; Reddy, Dereddi Raja S; Colantuoni, Elizabeth; Zanni, Jennifer M; Turnbull, Alison E; Nelliot, Archana; Ciesla, Nancy; Needham, Dale M

    2014-10-01

    Rehabilitation started early during an intensive care unit (ICU) stay is associated with improved outcomes and is the basis for many quality improvement (QI) projects showing important changes in practice. However, little evidence exists regarding whether such changes are sustainable in real-world practice. To evaluate the sustained effect of a quality improvement project on the timing of initiation of active physical therapy intervention in patients with acute lung injury (ALI). This was a pre-post evaluation using prospectively collected data involving consecutive patients with ALI admitted pre-quality improvement (October 2004-April 2007, n = 120) versus post-quality improvement (July 2009-July 2012, n = 123) from a single medical ICU. The primary outcome was time to first active physical therapy intervention, defined as strengthening, mobility, or cycle ergometry exercises. Among ICU survivors, more patients in the post-quality improvement versus pre-quality improvement group received physical therapy in the ICU (89% vs. 24%, P quality improvement versus pre-quality improvement group, there was a shorter median (interquartile range) time to first physical therapy (4 [2, 6] vs. 11 d [6, 29], P quality improvement period was associated with shorter time to physical therapy (adjusted hazard ratio [95% confidence interval], 8.38 [4.98, 14.11], P quality improvement period. The following variables were independently associated with a longer time to physical therapy: higher Sequential Organ Failure Assessment score (0.93 [0.89, 0.97]), higher FiO2 (0.86 [0.75, 0.99] for each 10% increase), use of an opioid infusion (0.47 [0.25, 0.89]), and deep sedation (0.24 [0.12, 0.46]). In this single-site, pre-post analysis of patients with ALI, an early rehabilitation quality improvement project was independently associated with a substantial decrease in the time to initiation of active physical therapy intervention that was sustained over 5 years. Over the entire pre

  5. Spermidine decreases Na⁺,K⁺-ATPase activity through NMDA receptor and protein kinase G activation in the hippocampus of rats.

    Science.gov (United States)

    Carvalho, Fabiano B; Mello, Carlos F; Marisco, Patricia C; Tonello, Raquel; Girardi, Bruna A; Ferreira, Juliano; Oliveira, Mauro S; Rubin, Maribel A

    2012-06-05

    Spermidine is an endogenous polyamine with a polycationic structure present in the central nervous system of mammals. Spermidine regulates biological processes, such as Ca(2+) influx by glutamatergic N-methyl-d-aspartate receptor (NMDA receptor), which has been associated with nitric oxide synthase (NOS) and cGMP/PKG pathway activation and a decrease of Na(+),K(+)-ATPase activity in rats' cerebral cortex synaptosomes. Na(+),K(+)-ATPase establishes Na(+) and K(+) gradients across membranes of excitable cells and by this means maintains membrane potential and controls intracellular pH and volume. However, it has not been defined whether spermidine modulates Na(+),K(+)-ATPase activity in the hippocampus. In this study we investigated whether spermidine alters Na(+),K(+)-ATPase activity in slices of hippocampus from rats, and possible underlying mechanisms. Hippocampal slices and homogenates were incubated with spermidine (0.05-10 μM) for 30 min. Spermidine (0.5 and 1 μM) decreased Na(+),K(+)-ATPase activity in slices, but not in homogenates. MK-801 (100 and 10 μM), a non-competitive antagonist of NMDA receptor, arcaine (0.5μM), an antagonist of the polyamine binding site at the NMDA receptor, and L-NAME (100μM), a NOS inhibitor, prevented the inhibitory effect of spermidine (0.5 μM). ODQ (10 μM), a guanylate cyclase inhibitor, and KT5823 (2 μM), a protein kinase G inhibitor, also prevented the inhibitory effect of spermidine on Na(+),K(+)-ATPase activity. Spermidine (0.5 and 1.0 μM) increased NO(2) plus NO(3) (NOx) levels in slices, and MK-801 (100 μM) and arcaine (0.5 μM) prevented the effect of spermidine (0.5 μM) on the NOx content. These results suggest that spermidine-induced decrease of Na(+),K(+)-ATPase activity involves NMDA receptor/NOS/cGMP/PKG pathway. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls

    Directory of Open Access Journals (Sweden)

    Davide Zanchi

    2017-12-01

    Full Text Available Background: Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals. Methods: 62 elderly individuals (41 females, including 41 controls (35 females and 21 middle cognitive impairment subjects (6 females, underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON with preserved cognition and deteriorating controls (dCON with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT for the 2-back condition and general linear model (GLM for the fMRI sequence. Results: At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN and of the Default Mode Network (DFM were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON. Conclusion: The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.

  7. Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines

    Directory of Open Access Journals (Sweden)

    Akram Jamshidzadeh

    2017-10-01

    Full Text Available Context: One of the most complained skin cares in ethnic skin like Asian women is hyperpigmentation, and lightening preparations have been long-standing desired. Due to the side effects of current drugs, medicinal plants have attracted more attentions as a source of novel drugs. Mazo (Quercus infectoria galls and Terminalia chebula fruits have been suggested in Persian Traditional Medicine as a safe treatment for hyperpigmentation. Aims: To evaluate the cytotoxicity and the effect on melanin synthesis in B16/F10 melanoma of Q. infectoria and T. chebula extracts. Methods: After collection and scientific authentication, plants were extracted by maceration method with methanol and were standardized based on total phenolic content. MTT assay and colorimetric method were used for cytotoxicity and determination of melanin content and tyrosinase activity in B16/F10 cells, respectively. Kojic acid was used as a reference compound. Results: Total phenolic content of Q. infectoria and T. chebula was determined as 287.34 ± 4.21 and 172.61 ± 8.67 mg gallic acid equivalent/g dried extract, respectively. Both plants decreased cell viability at 100 µg/mL and significantly reduced intercellular melanin to 66.25% and 71.1%, respectively in comparison to kojic acid (56.63% at 50 µg/mL. In the same concentration, 65.7% and 71.2% tyrosinase activity was inhibited by Q. infectoria and T. chebula, which significantly were different from control (p<0.001. Conclusions: These findings suggest that both plants especially Q. infectoria could inhibit melanogenesis in non-toxic concentrations and would be a good candidate for further studies.

  8. Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

    Science.gov (United States)

    Scheulen, M E; Hoensch, H; Kappus, H; Seeber, S; Schmidt, C G

    1987-01-01

    From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

  9. Cold or calculating? Reduced activity in the subgenual cingulate cortex reflects decreased emotional aversion to harming in counterintuitive utilitarian judgment

    Science.gov (United States)

    Wiech, Katja; Kahane, Guy; Shackel, Nicholas; Farias, Miguel; Savulescu, Julian; Tracey, Irene

    2013-01-01

    Recent research on moral decision-making has suggested that many common moral judgments are based on immediate intuitions. However, some individuals arrive at highly counterintuitive utilitarian conclusions about when it is permissible to harm other individuals. Such utilitarian judgments have been attributed to effortful reasoning that has overcome our natural emotional aversion to harming others. Recent studies, however, suggest that such utilitarian judgments might also result from a decreased aversion to harming others, due to a deficit in empathic concern and social emotion. The present study investigated the neural basis of such indifference to harming using functional neuroimaging during engagement in moral dilemmas. A tendency to counterintuitive utilitarian judgment was associated both with ‘psychoticism’, a trait associated with a lack of empathic concern and antisocial tendencies, and with ‘need for cognition’, a trait reflecting preference for effortful cognition. Importantly, only psychoticism was also negatively correlated with activation in the subgenual cingulate cortex (SCC), a brain area implicated in empathic concern and social emotions such as guilt, during counterintuitive utilitarian judgments. Our findings suggest that when individuals reach highly counterintuitive utilitarian conclusions, this need not reflect greater engagement in explicit moral deliberation. It may rather reflect a lack of empathic concern, and diminished aversion to harming others. PMID:23280149

  10. Acetylcholinesterase activity of electric eel is increased or decreased by selected monoterpenoids and phenylpropanoids in a concentration-dependent manner.

    Science.gov (United States)

    López, María Dolores; Campoy, Francisco J; Pascual-Villalobos, María Jesús; Muñoz-Delgado, Encarnación; Vidal, Cecilio J

    2015-03-05

    The profitable insecticidal action of monoterpenoids prompted us to test their efficiency against stored-grain beetle species, via inhibition of acetylcholinesterase (AChE). For this, we first studied the ability of the monoterpenoids geraniol, linalool, camphor, fenchone, carvone and γ-terpinene, besides the phenylpropanoids trans-anethole and estragole to inhibit Electrophorus AChE. The results indicated that while AChE activity increased (15-35%) with 40 μM geraniol, camphor, γ-terpinene and linalool, the activity decreased (60-40%) with 5mM carvone, γ-terpinene, and fenchone. The Km for AChE was 0.52 ± 0.02 mM in control assays, which fell to 0.28 ± 0.01 mM or 0.32 ± 0.01 mM in assays with 20 μM linalool or γ-terpinene added. In the millimolar range, the terpenoids behaved as weak inhibitors. Unexpectedly, AChE inhibition by camphor, carvone, γ-terpinene, and fenchone gave Hill numbers ranging 2.04-1.57, supporting the idea that AChE was able to lodge more than one monoterpenoid molecule. The plots of 1/v vs. 1/S at varying monoterpenoid provided straight lines, fenchone and γ-terpinene acting as competitive inhibitors and carvone and camphor as non-competitive inhibitors. Moreover, the secondary plots of the slope KM(app)/Vmax(app) vs. [I] and of 1/Vmax(app) vs. [I] gave parabolic curves, which lent support to the proposed capacity of AChE to bind more than one monoterpenoid molecule. The fitting of the curves to a second-order polynomial equation allowed us to calculate the inhibition constants for the interaction of AChE with fenchone, γ-terpinene, carvone and camphor. The previously unnoticed increase in AChE activity with monoterpenoids should be considered as a reminder when advising the use of essential oils of plants or their constituents as anti-AChE agents to attenuate pathological signs of Alzheimer's disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Nitrate decreases xanthine oxidoreductase-mediated nitrite reductase activity and attenuates vascular and blood pressure responses to nitrite.

    Science.gov (United States)

    Damacena-Angelis, Célio; Oliveira-Paula, Gustavo H; Pinheiro, Lucas C; Crevelin, Eduardo J; Portella, Rafael L; Moraes, Luiz Alberto B; Tanus-Santos, Jose E

    2017-08-01

    Nitrite and nitrate restore deficient endogenous nitric oxide (NO) production as they are converted back to NO, and therefore complement the classic enzymatic NO synthesis. Circulating nitrate and nitrite must cross membrane barriers to produce their effects and increased nitrate concentrations may attenuate the nitrite influx into cells, decreasing NO generation from nitrite. Moreover, xanthine oxidoreductase (XOR) mediates NO formation from nitrite and nitrate. However, no study has examined whether nitrate attenuates XOR-mediated NO generation from nitrite. We hypothesized that nitrate attenuates the vascular and blood pressure responses to nitrite either by interfering with nitrite influx into vascular tissue, or by competing with nitrite for XOR, thus inhibiting XOR-mediated NO generation. We used two independent vascular function assays in rats (aortic ring preparations and isolated mesenteric arterial bed perfusion) to examine the effects of sodium nitrate on the concentration-dependent responses to sodium nitrite. Both assays showed that nitrate attenuated the vascular responses to nitrite. Conversely, the aortic responses to the NO donor DETANONOate were not affected by sodium nitrate. Further confirming these results, we found that nitrate attenuated the acute blood pressure lowering effects of increasing doses of nitrite infused intravenously in freely moving rats. The possibility that nitrate could compete with nitrite and decrease nitrite influx into cells was tested by measuring the accumulation of nitrogen-15-labeled nitrite ( 15 N-nitrite) by aortic rings using ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS). Nitrate exerted no effect on aortic accumulation of 15 N-nitrite. Next, we used chemiluminescence-based NO detection to examine whether nitrate attenuates XOR-mediated nitrite reductase activity. Nitrate significantly shifted the Michaelis Menten saturation curve to the right, with a 3-fold increase in the

  12. Renal sodium retention in cirrhotic rats depends on glucocorticoid-mediated activation of mineralocorticoid receptor due to decreased renal 11beta-HSD-2 activity

    DEFF Research Database (Denmark)

    Thiesson, Helle; Jensen, Boye L; Bistrup, Claus

    2007-01-01

    Downregulation of the renal glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) during liver cirrhosis may allow activation of the mineralocorticoid receptor (MR) by glucocorticoids and contribute to sodium retention. We tested this hypothesis in male Wistar...... rats with decompensated liver cirrhosis and ascites 7 wk after bile duct ligation (BDL). Renal 11beta-HSD-2 mRNA, protein, and activity were significantly decreased in decompensated rats. The urinary Na(+)/K(+) ratio was reduced by 40%. Renal epithelial sodium channel (ENaC) mRNA and immunostaining...... were only slightly affected. Complete metabolic studies, including fecal excretion, showed that the BDL rats had avid renal sodium retention. Treatment of the BDL rats with dexamethasone suppressed endogenous glucocorticoid production, normalized total sodium balance and renal sodium excretion...

  13. Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive oxygen species generation and protein kinase C-α/δ activation.

    Directory of Open Access Journals (Sweden)

    Chen-Lung Ho

    Full Text Available Bamboo vinegar (BV, a natural liquid derived from the condensation produced during bamboo charcoal production, has been used in agriculture and as a food additive, but its application to immune modulation has not been reported. Here, we demonstrated that BV has anti-inflammatory activities both in vitro and in vivo. BV reduced inducible nitric oxide synthase expression and nitric oxide levels in, and interleukin-6 secretion by, lipopolysaccharide-activated macrophages without affecting tumor necrosis factor-α secretion and cyclooxygenase-2 expression. The mechanism for the anti-inflammatory effect of BV involved decreased reactive oxygen species production and protein kinase C-α/δ activation. Furthermore, creosol (2-methoxy-4-methylphenol was indentified as the major anti-inflammatory compound in BV. Impaired cytokine expression and NLR family, pyrin domain-containing 3 (NLRP3 inflammasome activation was seen in mice treated with creosol. These findings provide insights into how BV regulates inflammation and suggest that it may be a new source for the development of anti-inflammatory agents or a healthy supplement for preventing and ameliorating inflammation- and NLRP3 inflammasome-related diseases, including metabolic syndrome.

  14. Increasing physical activity and decreasing sedentary activity in adolescent girls – The Incorporating More Physical Activity and Calcium in Teens (IMPACT) study

    OpenAIRE

    Hergenroeder Albert; Kelder Steven H; Hoelscher Deanna M; Jones Desiree; Sharma Shreela V

    2008-01-01

    Abstract Background Lack of regular physical activity and consequent sub-optimal bone mass acquisition in youth has been implicated as a primary cause of adult-onset osteoporosis. IMPACT was a behavioral theory-based 1 1/2 year randomized controlled field study aimed at increasing bone accretion in middle school girls. The objective of this study was to determine the intervention effects of the IMPACT program upon key physical and sedentary activity endpoints among schools that participated i...

  15. Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

    Science.gov (United States)

    Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptos...

  16. Curcumin decreases the expression of Pokemon by suppressing the binding activity of the Sp1 protein in human lung cancer cells.

    Science.gov (United States)

    Cui, Jiajun; Meng, Xianfeng; Gao, Xudong; Tan, Guangxuan

    2010-03-01

    Pokemon, which stands for POK erythroid myeloid ontogenic factor, can regulate expression of many genes and plays an important role in tumorigenesis. Curcumin, a natural and non-toxic yellow compound, has capacity for antioxidant, free radical scavenger, anti-inflammatory properties. Recent studies shows it is a potential inhibitor of cell proliferation in a variety of tumour cells. To investigate whether curcumin can regulate the expression of Pokemon, a series of experiments were carried out. Transient transfection experiments demonstrated that curcumin could decrease the activity of the Pokemon promoter. Western blot analysis suggested that curcumin could significantly decrease the expression of the Pokemon. Overexpression of Sp1 could enhance the activity of the Pokemon promoter, whereas knockdown of Sp1 could decrease its activity. More important, we also found that curcumin could decrease the expression of the Pokemon by suppressing the stimulation of the Sp1 protein. Therefore, curcumin is a potential reagent for tumour therapy which may target Pokemon.

  17. Teaching Students to Request the Continuation of Routine Activities by Using Time Delay and Decreasing Physical Assistance in the Context of Chain Interruption.

    Science.gov (United States)

    Gee, Kathleen; And Others

    1991-01-01

    Three students (ages 5-10) with profound intellectual, sensory, and physical disabilities were taught to activate a communication device to request the continuation of activities in which they were involved. The intervention consisted of a consistent response interval and increasing time delay paired with decreasing physical assistance in…

  18. [Increase in cigarette smoking and decrease in the level of physical activity among Spanish adolescentes. AVENA study].

    Science.gov (United States)

    Tercedor, P; Martín-Matillas, M; Chillón, P; Pérez López, I J; Ortega, F B; Wärnberg, J; Ruiz, J R; Delgado, M

    2007-01-01

    Cigarette smoking among adolescents as well as the level of physical activity constitutes a public health care issue. The aim is knowing the relationship between cigarette smoking and practice of physical activity. Schooled Spanish adolescents 2859 Spanish adolescents (1357 boys, 1502 girls; age range: 13-18.5 years). A questionnaire is applied to know the level of cigarette smoking and four other questionnaires to know the level of physical activity during different periods. 40.8% of the adolescents stated not doing any physical activity at all, boys being more active than girls (p < 0.001). 29.9% of the adolescents stated usually smoking cigarettes, without differences by gender. Both active boys and girls stated smoking less (P < or = 0.01). The greater the age, the higher cigarette smoking and the lower the level of physical activity, both in boys and girls (p < 0.001). The level of physical activity is low, being even lower for girls. Cigarette smoking shows a negative relationship with the level of physical activity, the individuals more physically active being those smoking the less.

  19. Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice.

    Science.gov (United States)

    Hulmi, Juha J; Oliveira, Bernardo M; Silvennoinen, Mika; Hoogaars, Willem M H; Pasternack, Arja; Kainulainen, Heikki; Ritvos, Olli

    2013-07-15

    The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.

  20. Low-level activity of the trunk extensor muscles causes electromyographic manifestations of fatigue in absence of decreased oxygenation

    NARCIS (Netherlands)

    Dieën, J.H. van; Westebring van der; Putten, E.P.; Kingma, I.; Looze, M.P. de

    2009-01-01

    This study was designed to determine whether trunk extensor fatigue occurs during low-level activity and whether this is associated with a drop in muscle tissue oxygenation. Electromyography (EMG) feedback was used to impose constant activity in a part of the trunk extensor muscles. We hypothesized

  1. Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

    Science.gov (United States)

    Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

    2016-06-01

    Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Long-chain n-3 PUFA supplementation decreases physical activity during class time in iron-deficient South African school children.

    Science.gov (United States)

    Smuts, Cornelius M; Greeff, Jani; Kvalsvig, Jane; Zimmermann, Michael B; Baumgartner, Jeannine

    2015-01-28

    Both Fe deficiency and poor n-3 fatty acid status have been associated with behavioural changes in children. In the present study, we investigated the effects of Fe and DHA+EPA supplementation, alone or in combination, on physical activity during school days and on teacher-rated behaviour in healthy Fe-deficient school children. In a 2 × 2 factorial design, children (n 98, 6-11 years) were randomly assigned to receive (1) Fe (50 mg) plus DHA (420 mg)+EPA (80 mg), (2) Fe plus placebo, (3) placebo plus DHA+EPA or (4) placebo plus placebo as oral supplements (4 d/week) for 8.5 months. Physical activity was measured during four school days at baseline and endpoint using accelerometers, and data were stratified into morning class time (08.00-10.29 hours), break time (10.30-11.00 hours) and after-break class time (11.01-12.00 hours) for analysis. Classroom behaviour was assessed at endpoint using Conners' Teacher Rating Scales. DHA+EPA supplementation decreased physical activity counts during morning class time, increased sedentary physical activity, and decreased light- and moderate-intensity physical activities. Consistently, DHA+EPA supplementation increased sedentary physical activity and decreased light-intensity physical activity during after-break class time. Even though there were no treatment effects found on teacher-rated behaviour, lower physical activity during morning class time was associated with lower levels of teacher-rated hyperactivity and oppositional behaviour at endpoint. Despite a positive association between Fe status and physical activity during break time at baseline, Fe supplementation did not affect physical activity during break time and class time. Our findings suggest that DHA+EPA supplementation may decrease physical activity levels during class time, and further indicate that accelerometry might be a useful tool to assess classroom behaviour in healthy children.

  3. Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

    Directory of Open Access Journals (Sweden)

    Xin eQi

    2015-11-01

    Full Text Available Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with Internet gaming disorder (IGD, which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs without IGD were recruited, and the Balloon Analog Risk Task (BART was used in a functional magnetic resonance imaging (fMRI experiment to evaluate the modulation of the risk level (the probability of balloon explosion on brain activity during risky decisionmaking in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11 scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents.

  4. [A PARADIGM SHIFT IN THE PERCEPTION OF HEALTH MAINTENANCE FROM INCREASING PHYSICAL ACTIVITY TO DECREASING PHYSICAL INACTIVITY].

    Science.gov (United States)

    Rotman, Dani; Constantini, Naama

    2016-06-01

    Modern man spends most of his waking hours (50-70%) in one form or another of sedentary behavior, defined as activity conducted in a sitting or reclining position involving low energy expenditure. The remaining waking hours are spent performing low intensity physical activity (25-45%) and medium-high intensity physical activity (less than 5%): Despite this distribution, medical research has focused on the impact of increasing medium-high intensity physical activity and many health organizations' recommendations are in accordance. In recent years, research conducted has begun to examine the effect inactivity has on health and has shown that excess sedentary behaviour is an independent risk factor for a wide range of medical problems such as obesity, metabolic syndrome, poor cardiovascular health profile, diabetes mellitus, and possibly cancer. Although the higher risk brought on by sedentary behaviour is partially reduced by increasing medium-high intensity physical activity, it is not completely neutralized. One way to diminish the harm caused by long hours of sitting is to take short breaks during periods of prolonged sitting in order to walk. According to these findings, it is worthwhile to recommend reducing the hours spent in sedentary behaviour, or at least to take frequent short breaks ("activity snacks") during periods of prolonged sitting to get up and walk around.

  5. Serotonin depletion results in a decrease of the neuronal activation caused by rivastigmine in the rat hippocampus

    DEFF Research Database (Denmark)

    Kornum, Birgitte R; Weikop, Pia; Moller, Arne

    2006-01-01

    nicotinic receptors located at nerve terminals. The aim of the present study was to determine in which areas and to what extent 5-HT mediates the neuronal response to ACh release. For this purpose, neuronal activity was measured in rats with rivastigmine-induced elevated ACh levels after a 95% 5-HT...... depletion obtained by dosing p-chlorophenylalanine followed by D,L-fenfluramine. Neuronal activation was quantified by stereological measurements of c-Fos immunoreactivity. The brain areas examined were medial prefrontal cortex, septum, dorsal hippocampus, and dorsal raphe nucleus. Rivastigmine...... brain areas examined. It is concluded that 5-HT mediates part of the ACh-induced hippocampal neuronal activation, possibly mediated via locally released 5-HT....

  6. Extremely decreased release of prostaglandin E-like activity from chopped lung of ethyl linolenate-supplemented rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.; Fjalland, B.

    1983-01-01

    Three groups of weanling male rats were reared on a fat-free diet for 13 weeks. One group received only the fat-free diet (FF rats), the other 2 groups received the fat-free diet and a daily supplement of 2 energy% ethyl linoleate ([n-6] rats), or 2 energy% ethyl linolenate ([n-3] rats). The chop......). The chopped lung preparation was used to illustrate an in vitro prostaglandin formation. PGE-like activity was quantified on rat stomach strip. The release of PGE-like activity expressed as ng PGE-equivalent per g lung tissue (mean±SD) was 23±7,...

  7. Activation of gibberellin 2-oxidase 6 decreases active gibberellin levels and creates a dominant semi-dwarf phenotype in rice (Oryza sativa L.).

    Science.gov (United States)

    Huang, Jian; Tang, Ding; Shen, Yi; Qin, Baoxiang; Hong, Lilan; You, Aiqing; Li, Ming; Wang, Xin; Yu, Hengxiu; Gu, Minghong; Cheng, Zhukuan

    2010-01-01

    Gibberellin (GA) 2-oxidase plays a key role in the GA catabolic pathway through 2beta-hydroxylation. In the present study, we isolated a CaMV 35S-enhancer activation tagged mutant, H032. This mutant exhibited a dominant dwarf and GA-deficient phenotype, with a final stature that was less than half of its wild-type counterpart. The endogenous bioactive GAs are markedly decreased in the H032 mutant, and application of bioactive GAs (GA(3) or GA(4)) can reverse the dwarf phenotype. The integrated T-DNA was detected 12.8 kb upstream of the OsGA2ox6 in the H032 genome by TAIL-PCR. An increased level of OsGA2ox6 mRNA was detected at a high level in the H032 mutant, which might be due to the enhancer role of the CaMV 35S promoter. RNAi and ectopic expression analysis of OsGA2ox6 indicated that the dwarf trait and the decreased levels of bioactive GAs in the H032 mutant were a result of the up-regulation of the OsGA2ox6 gene. BLASTP analysis revealed that OsGA2ox6 belongs to the class III of GA 2-oxidases, which is a novel type of GA2ox that uses C20-GAs (GA(12) and/or GA(53)) as the substrates. Interestingly, we found that a GA biosynthesis inhibitor, paclobutrazol, positively regulated the OsGA2ox6 gene. Unlike the over-expression of OsGA2ox1, which led to a high rate of seed abortion, the H032 mutant retained normal flowering and seed production. These results indicate that OsGA2ox6 mainly affects plant stature, and the dominant dwarf trait of the H032 mutant can be used as an efficient dwarf resource in rice breeding. Copyright 2010 Institute of Genetics and Developmental Biology and the Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  8. Cinnamic acid-inhibited ribulose-1,5-bisphosphate carboxylase activity is mediated through decreased spermine and changes in the ratio of polyamines in cowpea.

    Science.gov (United States)

    Huang, Xingxue; Bie, Zhilong

    2010-01-01

    This study investigated the effects of cinnamic acid (CA) on ribulose-1,5-bisphosphate carboxylase (RuBPC) activity and the endogenous polyamine levels of cowpea leaves. The results show that 0.1 mM CA treatment decreased photosynthetic rate (P(n)) and RuBPC activity, but it did not affect the maximal photochemical efficiency of PSII (F(v)/F(m)), the actual photochemical efficiency of PSII (PhiPSII), intercellular CO(2) concentration (C(i)), and relative chlorophyll content. These suggest that the decrease in P(n) is at least partially attributed to a lowered RuBPC activity. In addition, 0.1 mM CA treatment increased the putrescine (Put) level, but decreased spermidine (Spd) and spermine (Spm) levels, thereby reducing the (Spd+Spm)/Put (PAs) ratio in the leaves. The exogenous application of 1 mM Spd markedly reversed these CA-induced effects for polyamine and partially restored the PAs ratio and RuBPC activity in leaves. Methylglyoxal-bis (guanylhydrazone) (MGBG), which is an inhibitor of S-adenosylmethionine decarboxylase (SAMDC), results in the inability of activated cells to synthesize Spd and exacerbates the negative effects induced by CA. The exogenous application of 1 mM D-arginine (D-Arg), which is an inhibitor of Put biosynthesis, decreased the levels of Put, but increased the PAs ratio and RuBPC activity in leaves. These results suggest that 0.1 mM CA inhibits RuBPC activity by decreasing the levels of endogenous free and perchloric acid soluble (PS) conjugated Spm, as well as the PAs ratio.

  9. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    van der Valk, Eline S.; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H.; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

    BACKGROUND: Health related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to

  10. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    Valk, E.S. Van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M de; Backx, F.J.; Hermus, A.R.M.M.; Zelissen, P.M.J.

    2016-01-01

    BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to

  11. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    Valk, E.S. van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M. de; Backx, F.J.G.; Hermus, A.R.M.M.; Zelissen, P.M.J.

    2016-01-01

    Background: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. Objective: The aim of this study was to

  12. Decrease in heart rate after longitudinal participation in the Groningen Active Living Model (GALM) recreational sports programme

    NARCIS (Netherlands)

    de Jong, Johan; Lemmink, Koen; Scherder, Erik; Stewart, Roy; King, Abby; Stevens, Martin

    2009-01-01

    The aim of this study was to investigate changes in heart rate during submaximal exercise as an index of cardiovascular function in older adults participating in the Groningen Active Living Model recreational sports programme who were sedentary or underactive at baseline. A repeated measurement

  13. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Voss, Kelsey; Amaya, Moushimi [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Mueller, Claudius [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Roberts, Brian [Leidos Health Life Sciences, 5202 Presidents Court, Suite 110, Frederick, MD (United States); Kehn-Hall, Kylene; Bailey, Charles [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States); Petricoin, Emanuel [Center for Applied Proteomics and Personalized Medicine, George Mason University, 10900 University Boulevard, Manassas, VA (United States); Narayanan, Aarthi, E-mail: anaraya1@gmu.edu [National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, 10650 Pyramid Place, Manassas, VA (United States)

    2014-11-15

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells.

  14. Inhibition of host extracellular signal-regulated kinase (ERK) activation decreases new world alphavirus multiplication in infected cells

    International Nuclear Information System (INIS)

    Voss, Kelsey; Amaya, Moushimi; Mueller, Claudius; Roberts, Brian; Kehn-Hall, Kylene; Bailey, Charles; Petricoin, Emanuel; Narayanan, Aarthi

    2014-01-01

    New World alphaviruses belonging to the family Togaviridae are classified as emerging infectious agents and Category B select agents. Our study is focused on the role of the host extracellular signal-regulated kinase (ERK) in the infectious process of New World alphaviruses. Infection of human cells by Venezuelan equine encephalitis virus (VEEV) results in the activation of the ERK-signaling cascade. Inhibition of ERK1/2 by the small molecule inhibitor Ag-126 results in inhibition of viral multiplication. Ag-126-mediated inhibition of VEEV was due to potential effects on early and late stages of the infectious process. While expression of viral proteins was down-regulated in Ag-126 treated cells, we did not observe any influence of Ag-126 on the nuclear distribution of capsid. Finally, Ag-126 exerted a broad-spectrum inhibitory effect on New World alphavirus multiplication, thus indicating that the host kinase, ERK, is a broad-spectrum candidate for development of novel therapeutics against New World alphaviruses. - Highlights: • VEEV infection activated multiple components of the ERK signaling cascade. • Inhibition of ERK activation using Ag-126 inhibited VEEV multiplication. • Activation of ERK by Ceramide C6 increased infectious titers of TC-83. • Ag-126 inhibited virulent strains of all New World alphaviruses. • Ag-126 treatment increased percent survival of infected cells

  15. Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant

    NARCIS (Netherlands)

    I.I.L. Berk-Planken (Ingrid); N. Hoogerbrugge (Nicoline); R.P. Stolk (Ronald); A.H. Bootsma (Aart); H. Jansen (Hans)

    2003-01-01

    textabstractOBJECTIVE: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the

  16. Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

    Science.gov (United States)

    Dursun, Polat; Demirtaş, Ezgi; Bayrak, Ahmet; Yarali, Hakan

    2006-01-01

    Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

  17. Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines.

    Science.gov (United States)

    Myers, Rachel; Grundy, Megan; Rowe, Cliff; Coviello, Christian M; Bau, Luca; Erbs, Philippe; Foloppe, Johann; Balloul, Jean-Marc; Story, Colin; Coussios, Constantin C; Carlisle, Robert

    2018-01-01

    The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US), can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox), cetuximab, adenovirus (Ad) and vaccinia virus (VV), representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a "cavitation test rig" was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene luciferase within the Ad and VV constructs tested here allowed the infectivity of these viruses to be easily quantified. Exposure to cavitation did not impact on the activity of either virus. These data provide compelling evidence that the US parameters used to safely and successfully delivery nanomedicines to tumors in preclinical models do not detrimentally impact on the

  18. Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats.

    Science.gov (United States)

    Dos Santos, Roger L; Dellacqua, Lais O; Delgado, Nathalie T B; Rouver, Wender N; Podratz, Priscila L; Lima, Leandro C F; Piccin, Mariela P C; Meyrelles, Silvana S; Mauad, Helder; Graceli, Jones B; Moyses, Margareth R

    2016-01-01

    Based on the antioxidant properties of pomegranate, this study was designed to investigate the effects of pomegranate peel extract on damage associated with hypertension and aging in a spontaneously hypertensive rat (SHR) model. The influence of pomegranate consumption was examined on systolic blood pressure (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress, and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d, with terminal experimental animal age being 8 and 32 wk, respectively, with either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed significant reduction in SBP and coronary ACE activity in both age groups. The levels of superoxide anion, a measure of oxidative stress, were significantly lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology demonstrated total increases in vascular wall areas were in the SHR group, and pomegranate peel extract diminished this effect. Pomegranate peel extract consumption conferred protection against hypertension in the SHR model. This finding was demonstrated by marked reduction in coronary ACE activity, oxidative stress, and vascular remodelling. In addition, treatment was able to reduce SBP in both groups. Evidence indicates that the use of pomegranate peel extract may prove beneficial in alleviating coronary heart disease.

  19. Benevolent sexist ideology attributed to an abusive partner decreases women's active coping responses to acts of sexual violence.

    Science.gov (United States)

    Durán, Mercedes; Moya, Miguel; Megías, Jesús L

    2014-05-01

    This article describes three studies in which we explored the influence of the sexist ideology attributed to the perpetrator on women's responses to hypothetical acts of sexual assault perpetrated by male intimate partners. In Study 1 (n = 83), college women read three sexual assault scenarios in the context of an intimate relationship. The male partner's sexist ideology (benevolent, hostile, or control) was manipulated within participants. Women showed less active responses when the partner had been described as a benevolent sexist man. This effect was replicated in Study 2 (n = 103), which showed a relationship between women's less active responses and the belief that benevolent sexist men are very attracted to and interested in their partners. Study 3 (n = 130) demonstrated experimentally that women's responses are less active when they are exposed to information that indicates that the perpetrator is both high in benevolent sexism and highly attracted to his victim than when the latter information is not provided. Results suggest that sexist ideology and particularly benevolent sexism-attributed to the perpetrator in this case-is highly important in women's reactions to acts of sexual violence perpetrated by male intimate partners.

  20. Activation of p44/42 in Human Natural Killer Cells Decreases Cell-surface Protein Expression: Relationship to Tributyltin-induced alterations of protein expression

    Science.gov (United States)

    Dudimah, Fred D.; Abraha, Abraham; Wang, Xiaofei; Whalen, Margaret M.

    2010-01-01

    Tributyltin (TBT) activates the mitogen activated protein kinase (MAPK), p44/42 in human natural killer (NK) cells. TBT also reduces NK cytotoxic function and decreases the expression of several NK-cell proteins. To understand the role that p44/42 activation plays in TBT-induced loss of NK cell function, we have investigated how selective activation of p44/42 by phorbol 12-myristate 13-acetate (PMA) affects NK cells. Previously we showed that PMA caused losses of lytic function similar to those seen with TBT exposures. Here we examined activation of p44/42 in the regulation of NK-cell protein expression and how this regulation may explain the protein expression changes seen with TBT exposures. NK cells exposed to PMA were examined for levels of cell-surface proteins, granzyme mRNA, and perforin mRNA expression. The expression of CD11a, CD16, CD18, and CD56 were reduced, perforin mRNA levels were unchanged and granzyme mRNA levels were increased. To verify that activation of p44/42 was responsible for the alterations seen in CD11a, CD16, CD18, and CD56 with PMA, NK cells were treated with the p44/42 pathway inhibitor (PD98059) prior to PMA exposures. In the presence of PD98059, PMA caused no decreases in the expression of the cell-surface proteins. Results of these studies indicate that the activation of p44/42 may lead to the loss of NK cell cytotoxic function by decreasing the expression of CD11a, CD16, CD18, and CD56. Further, activation of p44/42 appears to be at least in part responsible for the TBT-induced decreases in expression of CD16, CD18, and CD56. PMID:20883105

  1. Heparin (GAG-hed) inhibits LCR activity of Human Papillomavirus type 18 by decreasing AP1 binding

    International Nuclear Information System (INIS)

    Villanueva, Rita; Morales-Peza, Néstor; Castelán-Sánchez, Irma; García-Villa, Enrique; Tapia, Rocio; Cid-Arregui, Ángel; García-Carrancá, Alejandro; López-Bayghen, Esther; Gariglio, Patricio

    2006-01-01

    High risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line. Using in vivo and in vitro approaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA. We were able to record the antitumoral effect of GAG-hed in vivo by using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G 2 /M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR. Direct interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data suggest that GAG-hed could have

  2. Increases in the right dorsolateral prefrontal cortex and decreases the rostral prefrontal cortex activation after-8 weeks of focused attention based mindfulness meditation.

    Science.gov (United States)

    Tomasino, Barbara; Fabbro, Franco

    2016-02-01

    Mindfulness meditation is a form of attention control training. The training exercises the ability to repeatedly focus attention. We addressed the activation changes related to an 8-weeks mindfulness-oriented focused attention meditation training on an initially naïve subject cohort. Before and after training participants underwent an fMRI experiment, thus, although not strictly a cross over design, they served as their internal own control. During fMRI they exercised focused attention on breathing and body scan as compared to resting. We found increased and decreased activation in different parts of the prefrontal cortex (PFC) by comparing pre- vs. post-mindfulness training (MT) during breathing and body scan meditation exercises that were compared against their own resting state. In the post-MT (vs. pre-MT) meditation increased activation in the right dorsolateral PFC and in the left caudate/anterior insula and decreased activation in the rostral PFC and right parietal area 3b. Thus a brief mindfulness training caused increased activation in areas involved in sustaining and monitoring the focus of attention (dorsolateral PFC), consistent with the aim of mindfulness that is exercising focused attention mechanisms, and in the left caudate/anterior insula involved in attention and corporeal awareness and decreased activation in areas part of the "default mode" network and is involved in mentalizing (rostral PFC), consistent with the ability trained by mindfulness of reducing spontaneous mind wandering. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Comparison of specular H-atomic-beam intensity and C+ secondary-ion yield at thermally activated decrease of a carbon layer on a Ni(110) surface

    International Nuclear Information System (INIS)

    Kaarmann, H.; Hoinkes, H.; Wilsch, H.

    1983-01-01

    The thermally activated disappearance of a carbon layer on a Ni(110) surface was investigated by the scattering of atomic hydrogen and by secondary-ion mass spectrometry. Decreasing C coverage at surface temperatures kept constant in each case at values between 650 and 750 K resulted in an exponential decrease of specular H-beam intensity as well as C + secondary-ion yield. This decrease in both cases fits first-order kinetics (presumable diffusion into the bulk) with an identical rate constant as a function of surface temperature and results finally in a preexponential frequency ν = 10/sup() 10plus-or-minus1/ s -1 and an activation energy E/sub A/ = 1.8 +- 0.2 eV

  4. Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

    Science.gov (United States)

    Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

    2014-06-01

    The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

  5. Dietary fish oil replacement with palm or poultry oil increases fillet oxidative stability and decreases liver glutathione peroxidase activity in barramundi (Lates calcarifer).

    Science.gov (United States)

    Wan Ahmad, Wan A R; Stone, David A J; Schuller, Kathryn A

    2013-12-01

    Complete dietary fish oil replacement with palm or poultry oil in barramundi (Lates calcarifer) had no detrimental effects on growth or hepatosomatic index of juvenile fish up to an average size of ~50 g. However, it significantly decreased the omega-3 (n-3) long-chain polyunsaturated fatty acid content of the fish muscle (fillet) lipids. This was particularly true for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are recognised for their health beneficial effects in the human diet. As a result of their decreased EPA and DHA content, the peroxidation index of the muscle lipids was also decreased. This was associated with increased simulated retail storage shelf life as indicated by decreased thiobarbituric acid reactive substances in muscle samples from fish fed the palm or poultry oil-based diets. Concomitantly, glutathione peroxidase (GPx) activity, but not glutathione S-transferase (GST) activity or reduced glutathione concentration, was significantly reduced in the liver of barramundi fed the palm or poultry oil-based diets as compared with the fish fed the fish oil-based diet. Furthermore, GPx and GST activity were very low in muscle, much lower than in gastrointestinal tract, liver or swim bladder. Therefore, we propose that liver GPx activity may be a good predictor of fillet shelf life in barramundi and other fish species.

  6. Decreased Killing Activity of Micafungin Against Candida guilliermondii, Candida lusitaniae, and Candida kefyr in the Presence of Human Serum.

    Science.gov (United States)

    Saleh, Qasem; Kovács, Renátó; Kardos, Gábor; Gesztelyi, Rudolf; Kardos, Tamás; Bozó, Aliz; Majoros, László

    2017-09-01

    Currently, echinocandins are first-line drugs for treatment of invasive candidiasis. However, data on how serum influences killing activity of echinocandins against uncommon Candida species are limited. Therefore, the killing activity of micafungin in RPMI-1640 and in 50% serum was compared against Candida guilliermondii, Candida lusitaniae, and Candida kefyr. Minimum inhibitory concentration (MIC) ranges in RPMI-1640 were 0.5-1, 0.12-0.25, and 0.06-0.12 mg/L, respectively. In 50% serum, MICs increased 32- to 256-fold. In RPMI-1640 ≥ 0.25, ≥4, and 32 mg/L micafungin was fungicidal against all four C. kefyr (≤4.04 hours), two of three C. lusitaniae (≤16.10 hours), and two of three C. guilliermondii (≤12.30 hours), respectively. In 50% serum, all three species grew at ≤4 mg/L. Micafungin at 16-32 mg/L was fungicidal against all C. kefyr isolates (≤3.03 hours) and at 32 mg/L was fungistatic against one of three C. lusitaniae isolates. Two C. lusitaniae isolates and all three C. guilliermondii grew at all tested concentrations. Adding human serum to susceptibility test media drew attention to loss of fungicidal or fungistatic activity of micafungin in the presence of serum proteins, which is not predicted by MICs in case of C. kefyr and C. lusitaniae in RPMI-1640. Our results strongly suggest that micafungin and probably other echinocandins should be used with caution against rare Candida species.

  7. Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?

    Science.gov (United States)

    Biehl, Stefanie C; Merz, Christian J; Dresler, Thomas; Heupel, Julia; Reichert, Susanne; Jacob, Christian P; Deckert, Jürgen; Herrmann, Martin J

    2016-05-27

    Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. © The Author 2016. Published by Oxford University Press on behalf

  8. Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines

    Directory of Open Access Journals (Sweden)

    Myers R

    2018-01-01

    Full Text Available Rachel Myers,1 Megan Grundy,2 Cliff Rowe,1 Christian M Coviello,1 Luca Bau,2 Philippe Erbs,3 Johann Foloppe,3 Jean-Marc Balloul,3 Colin Story,1 Constantin C Coussios,2 Robert Carlisle2 1OxSonics Ltd, The Magdalen Centre, 2BUBBL, IBME, Department of Engineering Science, University of Oxford, Oxford, UK; 3Transgene SA, Illkirch-Graffenstaden, France Abstract: The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US, can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox, cetuximab, adenovirus (Ad and vaccinia virus (VV, representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a “cavitation test rig” was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene

  9. Perceived Occupational Stress is associated with Decreased Cortical Activity of the Prefrontal Cortex: A Multichannel Near-infrared Spectroscopy Study.

    Science.gov (United States)

    Chou, Po-Han; Lin, Wei-Hao; Hung, Chao-An; Chang, Chiung-Chih; Li, Wan-Rung; Lan, Tsuo-Hung; Huang, Min-Wei

    2016-12-13

    Despite an increasing number of reports on the associations between chronic occupational stress and structural and functional changes of the brain, the underlying neural correlates of perceived occupational stress is still not clear. Perceived stress reflects the extents to which situations are appraised as stressful at a given point in one's life. Using near-infrared spectroscopy, we investigated the associations between perceived occupational stress and cortical activity over the bilateral frontotemporal regions during a verbal fluency test. Sixty-eight participants (17 men, 51 women), 20-62 years of age were recruited. Perceived occupational stress was measured using the Chinese version of Job Content Questionnaire, and the Chinese version of the Copenhagen Burnout Inventory. We found statistically significant negative associations between occupational burnout and brain cortical activity over the fronto-polar and dorsolateral prefrontal cortex during the VFT (r = -0.343 to -0.464). In conclusion, our research demonstrated a possible neural basis of perceived occupational stress that are distributed across the prefrontal cortex.

  10. The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes.

    Science.gov (United States)

    Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S; Dringen, Ralf

    2017-11-01

    Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13 C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U- 13 C]glucose. The presence of metformin did not compromise the viability of cultured astrocytes during 4 hr of incubation, but almost doubled cellular glucose consumption and lactate release. Compared with control cells, the presence of metformin dramatically lowered the molecular 13 C carbon labeling (MCL) of the cellular TCA cycle intermediates citrate, α-ketoglutarate, succinate, fumarate, and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13 C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA cycling ratio in metformin-treated astrocytes. Finally, the oxygen consumption of mitochondria isolated from metformin-treated astrocytes was drastically reduced in the presence of complex I substrates, but not of complex II substrates. These data demonstrate that exposure to metformin strongly impairs complex I-mediated mitochondrial respiration in astrocytes, which is likely to cause the observed decrease in labeling of mitochondrial TCA cycle intermediates and the stimulation of glycolytic lactate production. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Twofold reduction of phosphofructokinase activity in Lactococcus lactis results in strong decreases in growth rate and in glycolytic flux

    DEFF Research Database (Denmark)

    Andersen, Heidi Winterberg; Solem, Christian; Hammer, Karin

    2001-01-01

    reduced. Surprisingly, the mutants still showed homolactic fermentation, which indicated that the limitation was different from standard glucose-limited conditions, One explanation could be that the reduced activity of phosphofructokinase resulted in the accumulation of sugar-phosphates. Indeed, when one...... kinase and lactate dehydrogenase remained closer to the wild-type level. In defined medium supplemented with glucose, the growth rate of the mutants was reduced to 57 to 70% of wild-type levels and the glycolytic flux was reduced to 62 to 76% of wild-type levels. In complex medium growth was even further...... of the mutants was starved for glucose in glucose-limited chemostat, the growth rate could gradually be increased to 195% of the growth fate observed in glucose-saturated batch culture, suggesting that phosphofructokinase does affect the concentration of upstream metabolites. The pools of glucose-6- phosphate...

  12. Decreasing the damage in smart structures using integrated online DDA/ISMP and semi-active control

    International Nuclear Information System (INIS)

    Karami, K; Amini, F

    2012-01-01

    Integrated structural health monitoring (SHM) and vibration control has been considered recently by researchers. Up to now, all of the research in the field of integrated SHM and vibration control has been conducted using control devices and control algorithms to enhance system identification and damage detection. In this study, online SHM is used to improve the performance of structural vibration control, unlike previous research. Also, a proposed algorithm including integrated online SHM and a semi-active control strategy is used to reduce both damage and seismic response of the main structure due to strong seismic disturbance. In the proposed algorithm the nonlinear behavior of the building structure is simulated during the excitation. Then, using the measured data and the damage detection algorithm based on identified system Markov parameters (DDA/ISMP), a method proposed by the authors, damage corresponding to axial and bending stiffness of all structural elements is identified. In this study, a 20 t MR damper is employed as a control device to mitigate both damage and dynamic response of the building structure. Also, the interaction between SHM and a semi-active control strategy is assessed. To illustrate the efficiency of the proposed algorithm, a two bay two story steel braced frame structure is used. By defining the damage index and damage rate index, the input current of the MR damper is generated using a fuzzy logic controller. The obtained results show that the possibility of smart building creation is provided using the proposed algorithm. In comparison to the widely used strategy of only vibration control, it is shown that the proposed algorithm is more effective. Furthermore, in the proposed algorithm, the total consumed current intensity and generated control forces are considerably less than for the strategy of only vibration control. (paper)

  13. Decreasing the damage in smart structures using integrated online DDA/ISMP and semi-active control

    Science.gov (United States)

    Karami, K.; Amini, F.

    2012-10-01

    Integrated structural health monitoring (SHM) and vibration control has been considered recently by researchers. Up to now, all of the research in the field of integrated SHM and vibration control has been conducted using control devices and control algorithms to enhance system identification and damage detection. In this study, online SHM is used to improve the performance of structural vibration control, unlike previous research. Also, a proposed algorithm including integrated online SHM and a semi-active control strategy is used to reduce both damage and seismic response of the main structure due to strong seismic disturbance. In the proposed algorithm the nonlinear behavior of the building structure is simulated during the excitation. Then, using the measured data and the damage detection algorithm based on identified system Markov parameters (DDA/ISMP), a method proposed by the authors, damage corresponding to axial and bending stiffness of all structural elements is identified. In this study, a 20 t MR damper is employed as a control device to mitigate both damage and dynamic response of the building structure. Also, the interaction between SHM and a semi-active control strategy is assessed. To illustrate the efficiency of the proposed algorithm, a two bay two story steel braced frame structure is used. By defining the damage index and damage rate index, the input current of the MR damper is generated using a fuzzy logic controller. The obtained results show that the possibility of smart building creation is provided using the proposed algorithm. In comparison to the widely used strategy of only vibration control, it is shown that the proposed algorithm is more effective. Furthermore, in the proposed algorithm, the total consumed current intensity and generated control forces are considerably less than for the strategy of only vibration control.

  14. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

    Science.gov (United States)

    Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

    2013-07-15

    C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

  15. Can changes in psychosocial factors and residency explain the decrease in physical activity during the transition from high school to college or university?

    Science.gov (United States)

    Van Dyck, Delfien; De Bourdeaudhuij, Ilse; Deliens, Tom; Deforche, Benedicte

    2015-04-01

    When students make the transition from high school to college or university, their physical activity (PA) levels decrease strongly. Consequently, it is of crucial importance to identify the determinants of this decline in PA. The study aims were to (1) examine changes in psychosocial factors in students during the transition from high school to college/university, (2) examine if changes in psychosocial factors and residency can predict changes in PA, and (3) investigate the moderating effects of residency on the relationship between changes in psychosocial factors and changes in PA. Between March 2008 and October 2010, 291 Flemish students participated in a longitudinal study, with baseline measurements during the final year of high school and follow-up measurements at the start of second year of college/university. At both time points, participants completed a questionnaire assessing demographics, active transportation, leisure-time sports, psychosocial variables, and residency. Repeated measures MANOVA analyses and multiple moderated hierarchic regression analyses were conducted. Modeling, self-efficacy, competition-related benefits, and health-related, external and social barriers decreased, while health-related benefits and time-related barriers increased from baseline to follow-up. Decreases in modeling and time-related barriers were associated with a decrease in active transportation (adjusted R(2) = 3.2%); residency, decreases in self-efficacy, competition-related benefits, and increases in health- and time-related barriers predicted a decrease in leisure-time sports (adjusted R(2) = 29.3%). Residency only moderated two associations between psychosocial factors and changes in PA. Residency and changes in psychosocial factors were mainly important to explain the decrease in leisure-time sports. Other factors such as distance to college/university are likely more important to explain the decrease in active transportation; these are worth exploring in

  16. Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST-Decreasing HMG-CoA Reductase Expression Via AMP-Activated Protein Kinase.

    Science.gov (United States)

    Han, Joon-Seung; Sung, Jong Hwan; Lee, Seung Kwon

    2017-11-01

    GINST, a hydrolyzed ginseng extract, has been reported to have antidiabetic effects and to reduce hyperglycemia and hyperlipidemia. Hypercholesterolemia is caused by diet or genetic factors and can lead to atherosclerosis and coronary heart disease. Thus, the purpose of this study is to determine whether GINST and the ginsenoside metabolite, IH-901 (compound K), reduce cholesterol synthesis in HepG2 cells and the signal transduction pathways involved. Concentrations of cholesterol were measured by using an enzymatic method. Expression levels of sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), peroxisome proliferators-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins α (C/EBPα), GAPDH, and phosphorylation of AMP-activated protein kinase α (AMPKα), protein kinase B (PKB, also known as Akt), and mechanistic target of rapamycin complex 1 (mTORC1) were measured using western blot. Total cholesterol concentration decreased after GINST treatment for 24 and 48 h. Expression of HMGCR decreased more with GINST than with the inhibitors, U18666A and atorvastatin, after 48 h in a dose-dependent manner. Phosphorylation of AMPKα increased 2.5x by GINST after 360 min of treatment, and phosphorylation of Akt decreased after 120 and 360 min. We separated compound K from GINST extracts flash chromatography. Compound K decreased cholesterol synthesis in HepG2 cells at 24 and 48 h. Therefore, we conclude that GINST inhibits cholesterol synthesis in HepG2 cells by decreasing HMGCR expression via AMPKα activation. GINST, a hydrolyzed ginseng extract, can inhibit cholesterol synthesis in liver cells via activation of AMPKα. IH-901 (compound K), which is the main component with bioactivity in GINST, also has anticholesterol effects. Thus, we suggest that GINST can be used to reduce hypercholesterolemia. © 2017 Institute of Food Technologists®.

  17. GPR55 receptor antagonist decreases glycolytic activity in PANC-1 pancreatic cancer cell line and tumor xenografts.

    Science.gov (United States)

    Bernier, Michel; Catazaro, Jonathan; Singh, Nagendra S; Wnorowski, Artur; Boguszewska-Czubara, Anna; Jozwiak, Krzysztof; Powers, Robert; Wainer, Irving W

    2017-11-15

    The Warburg effect is a predominant metabolic pathway in cancer cells characterized by enhanced glucose uptake and its conversion to l-lactate and is associated with upregulated expression of HIF-1α and activation of the EGFR-MEK-ERK, Wnt-β-catenin, and PI3K-AKT signaling pathways. (R,R')-4'-methoxy-1-naphthylfenoterol ((R,R')-MNF) significantly reduces proliferation, survival, and motility of PANC-1 pancreatic cancer cells through inhibition of the GPR55 receptor. We examined (R,R')-MNF's effect on glycolysis in PANC-1 cells and tumors. Global NMR metabolomics was used to elucidate differences in the metabolome between untreated and (R,R')-MNF-treated cells. LC/MS analysis was used to quantify intracellular concentrations of β-hydroxybutyrate, carnitine, and l-lactate. Changes in target protein expression were determined by Western blot analysis. Data was also obtained from mouse PANC-1 tumor xenografts after administration of (R,R')-MNF. Metabolomics data indicate that (R,R')-MNF altered fatty acid metabolism, energy metabolism, and amino acid metabolism and increased intracellular concentrations of β-hydroxybutyrate and carnitine while reducing l-lactate content. The cellular content of phosphoinositide-dependent kinase-1 and hexokinase 2 was reduced consistent with diminished PI3K-AKT signaling and glucose metabolism. The presence of the GLUT8 transporter was established and found to be attenuated by (R,R')-MNF. Mice treated with (R,R')-MNF had significant accumulation of l-lactate in tumor tissue relative to vehicle-treated mice, together with reduced levels of the selective l-lactate transporter MCT4. Lower intratumoral levels of EGFR, pyruvate kinase M2, β-catenin, hexokinase 2, and p-glycoprotein were also observed. The data suggest that (R,R')-MNF reduces glycolysis in PANC-1 cells and tumors through reduced expression and function at multiple controlling sites in the glycolytic pathway. © 2017 UICC.

  18. Hydrogen sulphide decreases IL-1β-induced activation of fibroblast-like synoviocytes from patients with osteoarthritis

    Science.gov (United States)

    Sieghart, Daniela; Liszt, Melissa; Wanivenhaus, Axel; Bröll, Hans; Kiener, Hans; Klösch, Burkhard; Steiner, Günter

    2015-01-01

    Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA. PMID:25312962

  19. Connexin30-deficient mice show increased emotionality and decreased rearing activity in the open-field along with neurochemical changes.

    Science.gov (United States)

    Dere, E; De Souza-Silva, M A; Frisch, C; Teubner, B; Söhl, G; Willecke, K; Huston, J P

    2003-08-01

    Gap-junction channels in the brain, formed by connexin (Cx) proteins with a distinct regional/cell-type distribution, allow intercellular electrical and metabolic communication. In astrocytes, mainly the connexins 43, 26 and 30 are expressed. In addition, connexin30 is expressed in ependymal and leptomeningeal cells, as well as in skin and cochlea. The functional implications of the astrocytic gap-junctional network are not well understood and evidence regarding their behavioural relevance is lacking. Thus, we have tested groups of Cx30-/-, Cx30+/-, and Cx30+/+ mice in the open-field, an object exploration task, in the graded anxiety test and on the rotarod. The Cx30-/- mice showed reduced exploratory activity in terms of rearings but not locomotion in the open-field and object exploration task. Furthermore, Cx30-/- mice exhibited anxiogenic behaviour as shown by higher open-field centre avoidance and corner preference. Graded anxiety test and rotarod performance was similar across groups. The Cx30-/- mice had elevated choline levels in the ventral striatum, possibly related to their aberrant behavioural phenotypes. The Cx30+/- mice had lower dopamine and metabolite levels in the amygdala and ventral striatum and lower hippocampal 5-hydroxyindole acid (5-HIAA) concentrations relative to Cx30+/+ mice. Furthermore, the Cx30+/- mice had lower acetylcholine concentrations in the ventral striatum and higher choline levels in the neostriatum, relative to Cx30+/+ mice. Our data suggest that the elimination of connexin30 can alter the reactivity to novel environments, pointing to the importance of gap-junctional signalling in behavioural processes.

  20. Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity.

    Science.gov (United States)

    Sullivan, Elinor L; Shearin, Jean; Koegler, Frank H; Cameron, Judy L

    2012-04-01

    The effect of hormone replacement therapy (HRT) on body weight in postmenopausal women is controversial, with studies reporting an increase, a decrease, and no change in body weight. To examine estrogen receptor actions on body weight, we investigated the effects of treatment with a selective estrogen receptor modulator (SERM) on body weight, food intake, and activity and metabolic rate in a nonhuman primate model. Eighteen ovariectomized female rhesus monkeys were treated with a nonsteroidal SERM (GSK232802A, 5 mg/kg po) for 3 mo. GSK232802A decreased lutenizing hormone (P Physical activity increased during the 3rd mo of treatment (P = 0.04). Baseline activity level and the change in activity due to treatment were correlated, with the most sedentary individuals exhibiting increased physical activity during the 1st mo of treatment (P = 0.02). Metabolic rate did not change (P = 0.58). These results indicate that GSK232802A treatment reduces body weight and adiposity in ovariectomized nonhuman primates by suppressing food intake and increasing activity, particularly in the most sedentary individuals. These findings suggest that SERM treatment may counteract weight gain in postmenopausal women.

  1. Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract.

    Science.gov (United States)

    Kon, Risako; Ikarashi, Nobutomo; Nagoya, Chika; Takayama, Tomoko; Kusunoki, Yoshiki; Ishii, Makoto; Ueda, Harumi; Ochiai, Wataru; Machida, Yoshiaki; Sugita, Kazuyuki; Sugiyama, Kiyoshi

    2014-02-27

    Aquaporin-3 (AQP3) is expressed in mucosal epithelial cells in the colon and is important for regulating fecal water content. We examined the role of AQP3 in the laxative effect of rhubarb extract. After orally administering rhubarb extract or its major component (sennoside A) to rats, the fecal water content, AQP3 expression and prostaglandin E2 (PGE2) concentrations in the colon were examined. The mechanism by which sennoside A decreases the expression of AQP3 was examined using the human colon cancer HT-29 cells and macrophage-derived Raw264.7 cells. During diarrhea by rhubarb extract administration, the PGE2 levels in the colon increased while the AQP3 expression significantly decreased. Similar changes were also observed when sennoside A was administered. When sennoside A or its metabolites, rheinanthrone and rhein were added to Raw264.7 cells, a significant increase in the PGE2 concentration was observed only in cells treated with rheinanthrone. Fifteen minutes after adding PGE2 to the HT-29 cells, the AQP3 expression decreased to approximately 40% of the control. When pretreated with indomethacin, sennoside A neither decreased the AQP3 expression nor induced diarrhea. Sennoside A may decrease AQP3 expression in the colon to inhibit water transport from the luminal to the vascular side, leading to a laxative effect. The decreases in the levels of AQP3 are caused by rheinanthrone, which is a metabolite of sennoside A, this metabolite activates the macrophages in the colon and increases the secretion of PGE2; PGE2 acts as a paracrine factor and decreases AQP3 expression in colon mucosal epithelial cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Decreasing population blood pressure is not mediated by changes in habitual physical activity. Results from 15 years of follow-up

    DEFF Research Database (Denmark)

    Andersen, UO; Jensen, Gorm Boje

    2007-01-01

    of follow-up. This decrease leads to significant reductions in cardiovascular (CV) and cerebrovascular risk. The major aim of the present study was to evaluate the effect of habitual physical activity on PBP. Design. Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random...... population sample. Three surveys were performed with 15 years of follow-up. Methods. BP was measured under standardized circumstances. A questionnaire concerning physical exercise was completed. Two scales were used, describing physical activity at work and during leisure-time, respectively. Results. Most...... of the subjects belonged to the sedentary or low physical activity categories. The population did not change physical activity habits during the observation time. There was no significant difference in either systolic or diastolic BP between the categories. Conclusions. The previously observed reduction in PBP...

  3. Decreasing population blood pressure is not mediated by changes in habitual physical activity. Results from 15 years of follow-up

    DEFF Research Database (Denmark)

    Andersen, UO; Jensen, Gorm Boje

    2007-01-01

    population sample. Three surveys were performed with 15 years of follow-up. Methods. BP was measured under standardized circumstances. A questionnaire concerning physical exercise was completed. Two scales were used, describing physical activity at work and during leisure-time, respectively. Results. Most...... of follow-up. This decrease leads to significant reductions in cardiovascular (CV) and cerebrovascular risk. The major aim of the present study was to evaluate the effect of habitual physical activity on PBP. Design. Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random...... of the subjects belonged to the sedentary or low physical activity categories. The population did not change physical activity habits during the observation time. There was no significant difference in either systolic or diastolic BP between the categories. Conclusions. The previously observed reduction in PBP...

  4. A qualitative examination of factors related to the decrease in physical activity behavior in adolescent girls during the transition from primary to secondary school.

    Science.gov (United States)

    Knowles, Ann-Marie; Niven, Ailsa; Fawkner, Samantha

    2011-11-01

    Quantitative research has suggested that the decline in physical activity levels for adolescent girls is most marked during the transition from primary school to secondary school yet understanding the contributing factors for this decline may be advanced through qualitative research methods to gain an individual perspective of the girls' school transition experience. This study explored factors related to the decrease in physical activity behavior in 14 adolescent girls (mean age = 13.6 ± 0.3 years) during the transition between primary and secondary school through the use of narrative interviews and interpretative phenomenological analysis. The findings suggested that a change in the environment was central to understanding the decline in physical activity levels since primary school. During secondary school, a positive environment can be created by ensuring a choice of activities in Physical Education lessons; allowing a girls-only environment, to reduce the focus on competence and competition, and recognizing the importance of social support. These could enhance self-perceptions, reduce self-presentational concerns, increase enjoyment, and subsequently reduce the decrease in physical activity behavior during this key transitional period.

  5. Disease activity decrease is associated with improvement in work productivity over 1 year in early axial spondyloarthritis (SPondyloArthritis Caught Early cohort).

    Science.gov (United States)

    van Lunteren, Miranda; Ez-Zaitouni, Zineb; Fongen, Camilla; Landewé, Robert; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A

    2017-12-01

    To assess if a change in disease activity is associated with a change in work productivity loss (WPL) over 1 year in early axial SpA (axSpA) patients. Baseline and 1 year data of axSpA patients in the SPondyloArthritis Caught Early cohort were analysed. Linear regression models were built explaining the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS) over time by the change in absenteeism, presenteeism, WPL and activity impairment over time. Effect modification and confounding were tested for age, gender, arm of Assessment of SpondyloArthritis international Society classification criteria, HLA-B27, duration of chronic back pain, profession and medication. At baseline, in 105 axSpA patients (48% female, mean age 30.8 years, mean symptom duration 13.6 months, 92% HLA-B27 positive, 24% radiographic sacroiliitis), the mean ASDAS was 2.4 (s.d. 1.0), absenteeism 9% (s.d. 23), presenteeism 33% (s.d. 28), WPL 36% (s.d. 30) and activity impairment 37% (s.d. 25). After 1 year, the mean ASDAS decreased to 2.0 (s.d. 0.8) and absenteeism, presenteeism, WPL and activity impairment improved to 6% (s.d. 22), 26% (s.d. 26), 27% (s.d. 29) and 27% (s.d. 26), respectively. Models showed that if ASDAS decreased 1 unit, absenteeism, presenteeism, WPL and activity impairment improved by 5, 17, 16 and 18%, respectively. The impact of disease activity on work productivity was higher in patients with shorter symptom duration and the impact on absenteeism was higher in patients starting pharmacological treatment. In early axSpA patients, work productivity and daily activities are seriously impacted at baseline and 1 year. However, decreasing disease activity is associated with marked improvements in work productivity and daily activities. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. Acrolein, an I-κBα-independent downregulator of NF-κB activity, causes the decrease in nitric oxide production in human malignant keratinocytes.

    Science.gov (United States)

    Moon, Ki-Young

    2011-05-01

    Acrolein, a reactive electrophilic α, β-unsaturated aldehyde, is known to be an alkylating chemical carcinogen. The effect of acrolein on the activation of NF-κB in human malignant epidermal keratinocytes was examined to elucidate the molecular mechanism associated with this NF-κB-acrolein regulation and its consecutive sequence, nitric oxide (NO) production. Acrolein significantly downregulated the cellular NF-κB activity up to 60% compared with control as well as the lipopolysaccharide (LPS)-induced NO production in a dose response manner at concentrations of 10~30 μM. To investigate the regulatory mechanism associated with this NF-κB-acrolein downregulation, the relative level of phosphorylation of I-κBα (serines-32 and -36), a principle regulator of NF-κB activation, represented by acrolein, was quantified. Acrolein inhibited NF-κB activity without altering cellular levels of the phosphorylated and nonphosphorylated forms of I-κBα, implying that the downregulatory effect of acrolein on cellular NF-κB activity in human skin cells is an I-κBα-independent activation pathway. The results suggests that acrolein causes the decrease in nitric oxide production as an I-κBα-independent downregulator of NF-κB activity in human malignant keratinocytes, and acrolein-induced carcinogenesis may be associated with the modulation of cellular NF-κB activity.

  7. Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

    Science.gov (United States)

    Schimunek, Lukas; Serve, Rafael; Teuben, Michel P. J.; Störmann, Philipp; Auner, Birgit; Woschek, Mathias; Pfeifer, Roman; Horst, Klemens; Simon, Tim-P.; Kalbitz, Miriam; Sturm, Ramona; Pape, Hans-C.; Hildebrand, Frank; Marzi, Ingo

    2017-01-01

    In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased

  8. The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

    Science.gov (United States)

    De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

    2016-11-01

    d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Decreasing population blood pressure is not mediated by changes in habitual physical activity. Results from 15 years of follow-up.

    Science.gov (United States)

    Andersen, Ulla Overgaard; Jensen, Gorm

    2007-01-01

    Population blood pressure (PBP) is the average BP shared by all members of a population. In PBP research, the main focus is on the great majority of individuals who are healthy in respect to blood pressure. From previous studies, we know that PBP decreased 2 mmHg during 15 years of follow-up. This decrease leads to significant reductions in cardiovascular (CV) and cerebrovascular risk. The major aim of the present study was to evaluate the effect of habitual physical activity on PBP. Copenhagen City Heart Study is a longitudinal epidemiological study of CV risk in a random population sample. Three surveys were performed with 15 years of follow-up. BP was measured under standardized circumstances. A questionnaire concerning physical exercise was completed. Two scales were used, describing physical activity at work and during leisure-time, respectively. Most of the subjects belonged to the sedentary or low physical activity categories. The population did not change physical activity habits during the observation time. There was no significant difference in either systolic or diastolic BP between the categories. The previously observed reduction in PBP is not explained by a change in the population physical activity habits. This fact illustrates the difference between the high-risk strategy and the population strategy. In the first, the preventive strategy identifies hypertensive individuals and offers them antihypertensive medication and lifestyle modulation such as more and regular physical activity to improve blood pressure and lower individual CV and cerebrovascular risk. In contrast, the "population strategy" seeks to control the determinants of incidence in the population as a whole. This paper demonstrates that physical activity is not a determinant of PBP.

  10. Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart.

    OpenAIRE

    Ping, P; Gelzer-Bell, R; Roth, D A; Kiel, D; Insel, P A; Hammond, H K

    1995-01-01

    To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling as...

  11. Perinatal exposure to BDE-99 causes decreased protein levels of cyclin D1 via GSK3β activation and increased ROS production in rat pup livers.

    Science.gov (United States)

    Blanco, Jordi; Mulero, Miquel; Domingo, Jose L; Sanchez, Domènec J

    2014-02-01

    We here examined the potential liver toxicity in rat pups from dams exposed during the gestational and lactation periods to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Dams were exposed to 0, 1, and 2mg/kg/day of BDE-99 from gestation day 6 to postnatal day 21. When the pups were weaning, the liver from 1 pup of each litter was excised to evaluate oxidative stress markers and the messenger RNA (mRNA) expression of multiple cytochrome P450 (CYP) isoforms. To determine whether thyroid hormone (TH) was disrupted, the protein and mRNA expressions of several TH receptor (TR) isoforms, as well as the protein levels of cyclin D1 and the phosphorylated protein kinases Akt and glycogen synthase kinase 3 beta (GSK3β), were evaluated. Perinatal exposure to BDE-99 produced decreased levels of cyclin D1 in rat pup livers. A decrease in the active form of Akt and an increase in the active form of GSK3β were observed. The decreased Akt pathway may be due to a potential disruption of the nongenomic actions of TH by BDE-99 and its metabolites. This possible TH disruption was noted as a decrease in TR isoforms expression. By contrast, we observed an upregulation of CYP2B1 gene expression, which is correlated with an increase in reactive oxygen species production. This outcome indicates activation of the nuclear constitutive androstane receptor, which could induce the expression of other enzymes capable of metabolizing TH. The present findings support the hypothesis that perinatal exposure to PBDEs, at levels found in humans, may have serious implications for metabolic processes in rat pup livers.

  12. Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway.

    Science.gov (United States)

    Abdoel, Nursamaa; Brun, Susana; Bracho, Carmen; Rodríguez, Martín A; Blasini, Ana M

    2012-03-01

    Systemic lupus erythematosus (SLE) is characterized by abnormal signal transduction mechanisms in T lymphocytes. Linker for activation of T cells (LAT) couples TCR/CD3 activation with downstream signaling pathways. We reported diminished ERK 1/2 kinase activity in TCR/CD3 stimulated lupus T cells. In this study we evaluated the expression, phosphorylation, lipid raft and immunological synapse (IS) localization and colocalization of LAT with key signalosome molecules. We observed a diminished expression and an abnormal localization of LAT in lipid rafts and at the IS in activated lupus T cells. LAT phosphorylation, capture by GST-Grb2 fusion protein, and coupling to Grb2 and PLCγ1, was similar in healthy control and lupus T cells. Our results suggest that an abnormal localization of LAT within lipid rafts and its accelerated degradation after TCR/CD3 activation may compromise the assembly of the LAT signalosome and downstream signaling pathways required for full MAPK activation in lupus T cells. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state.

    Science.gov (United States)

    Huchzermeyer, Christine; Albus, Klaus; Gabriel, Hans-Jürgen; Otáhal, Jakub; Taubenberger, Nando; Heinemann, Uwe; Kovács, Richard; Kann, Oliver

    2008-01-30

    Gamma oscillations have been implicated in higher cognitive processes and might critically depend on proper mitochondrial function. Using electrophysiology, oxygen sensor microelectrode, and imaging techniques, we investigated the interactions of neuronal activity, interstitial pO2, and mitochondrial redox state [NAD(P)H and FAD (flavin adenine dinucleotide) fluorescence] in the CA3 subfield of organotypic hippocampal slice cultures. We find that gamma oscillations and spontaneous network activity decrease significantly at pO2 levels that do not affect neuronal population responses as elicited by moderate electrical stimuli. Moreover, pO2 and mitochondrial redox states are tightly coupled, and electrical stimuli reveal transient alterations of redox responses when pO2 decreases within the normoxic range. Finally, evoked redox responses are distinct in somatic and synaptic neuronal compartments and show different sensitivity to changes in pO2. We conclude that the threshold of interstitial pO2 for robust CA3 network activities and required mitochondrial function is clearly above the "critical" value, which causes spreading depression as a result of generalized energy failure. Our study highlights the importance of a functional understanding of mitochondria and their implications on activities of individual neurons and neuronal networks.

  14. Decreased activation of placental mTOR family members is associated with the induction of intrauterine growth restriction by secondhand smoke in the mouse.

    Science.gov (United States)

    Mejia, Camilo; Lewis, Josh; Jordan, Clinton; Mejia, Juan; Ogden, Connor; Monson, Troy; Winden, Duane; Watson, Marc; Reynolds, Paul R; Arroyo, Juan A

    2017-02-01

    Cigarette smoke is known to be a risk for the development of intrauterine growth restriction (IUGR). Our objective was to assess the effects of secondhand smoke (SHS) during pregnancy and to what extent it regulates the activation of mTOR family members and murine trophoblast invasion. Mice were treated to SHS for 4 days. Placental and fetal weights were recorded at the time of necropsy. Immunohistochemistry was used to determine the level of placental trophoblast invasion. Western blots were utilized to assess the activation of caspase 3, XIAP, mTOR, p70 and 4EBP1 in treated and control placental lysates. As compared to controls, treated animals showed: (1) decreased placental (1.4-fold) and fetal (2.3-fold) weights (p smoke extract (CSE). Similar to primary smoking, SHS may induce IUGR via decreased activation of the mTOR family of proteins in the placenta. Increased activation of the placental XIAP protein could be a survival mechanism for abnormal trophoblast cells during SHS exposure. Further, CSE reduced trophoblast invasion, suggesting a direct causative effect of smoke on susceptible trophoblast cells involved in IUGR progression. These results provide important insight into the physiological consequences of SHS exposure and smoke-mediated placental disease.

  15. Bupropion sustained release treatment decreases craving for video games and cue-induced brain activity in patients with Internet video game addiction.

    Science.gov (United States)

    Han, Doug Hyun; Hwang, Jun Won; Renshaw, Perry F

    2010-08-01

    Bupropion has been used in the treatment of patients with substance dependence based on its weak inhibition of dopamine and norepinephrine reuptake. We hypothesized that 6 weeks of bupropion sustained release (SR) treatment would decrease craving for Internet game play as well as video game cue-induced brain activity in patients with Internet video game addiction (IAG). Eleven subjects who met criteria for IAG, playing StarCraft (>30 hr/week), and eight healthy comparison subjects (HC) who had experience playing StarCraft (game, and the severity of Internet addiction were evaluated by Beck Depression Inventory, self-report of craving on a 7-point visual analogue scale, and Young's Internet Addiction Scale, respectively. In response to game cues, IAG showed higher brain activation in left occipital lobe cuneus, left dorsolateral prefrontal cortex, and left parahippocampal gyrus than HC. After a 6 week period of bupropion SR, craving for Internet video game play, total game play time, and cue-induced brain activity in dorsolateral prefrontal cortex were decreased in the IAG. We suggest that bupropion SR may change craving and brain activity in ways that are similar to those observed in individuals with substance abuse or dependence. PsycINFO Database Record 2010 APA, all rights reserved.

  16. Activation of Liver X Receptor Decreases Atherosclerosis in Ldlr−/− mice in the Absence of ABCA1 and ABCG1 in Myeloid Cells

    Science.gov (United States)

    Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

    2014-01-01

    Objective Liver X Receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly up-regulate genes involved in reverse cholesterol transport (RCT) and (2) exert anti-inflammatory effects mediated by transrepression of NFκB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate RCT, would abolish the beneficial effects of LXR activation on atherosclerosis. Approach and Results LXR activator T0901317 (T0) substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr−/− mice were transplanted with Abca1−/−Abcg1−/− or wild-type bone marrow (BM) and fed a Western-type diet (WTD) for 6 weeks with or without T0 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0 markedly decreased lesion area, complexity and inflammatory cell infiltration in the Abca1−/−Abcg1−/− BM transplanted mice. To investigate whether this was due to macrophage Abca1/g1 deficiency, Ldlr−/− mice were transplanted with LysmCreAbca1fl/flAbcg1fl/fl or Abca1fl/flAbcg1fl/fl BM and fed WTD with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups and the decrease was more prominent in the LysmCreAbca1fl/flAbcg1fl/fl group. Conclusions The results suggest that anti-inflammatory effects of LXR activators are of key importance to their anti-atherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to trans-repress inflammatory genes. PMID:24311381

  17. Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

    DEFF Research Database (Denmark)

    Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

    2016-01-01

    was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

  18. Heart rate variability reveals that a decrease in parasympathetic ('rest-and-digest') activity dominates autonomic stress responses in a free-living seabird.

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    Müller, Martina S; Vyssotski, Alexei L; Yamamoto, Maki; Yoda, Ken

    2017-10-01

    The autonomic stress response, often referred to as the 'fight-or-flight' response, is a highly conserved physiological reaction to stress in vertebrates that occurs via a decrease in parasympathetic (PNS) activity, which promotes self-maintenance 'rest and digest' processes, and an increase in sympathetic (SNS) activity, which prepares an animal for danger ('fight-or-flight'). Though the PNS and SNS both innervate most organs, they often control different tissues and functions within those organs (though the pacemaker of the heart is controlled by both). Moreover the PNS and SNS are regulated independently. Yet until now, most studies of autonomic stress responses in non-model species focused only on the SNS response. We used external electrocardiogram loggers to measure heart rate and heart rate variability indexes that reflect PNS and SNS activity in a seabird, the Streaked Shearwater (Calonectris leucomelas), during the stress of handling, and during recovery in the nest burrow or during restraint in a cloth bag. We show for the first time in a free-living animal that the autonomic stress response is mediated primarily by a rapid decrease in PNS activity: handling stress induced a large and long-lasting depression of PNS 'rest-and-digest' activity that required two hours to recover. We also found evidence for a substantially smaller and shorter-lasting SNS 'fight-or-flight' response. Confinement in a cloth bag was less stressful for birds than handling, but more stressful than recovering in nest burrows. We show that quantifying autonomic activity from heart rate variability is effective for non-invasively studying stress physiology in free-living animals. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. EXERCISES THAT FACILITATE OPTIMAL HAMSTRING AND QUADRICEPS CO-ACTIVATION TO HELP DECREASE ACL INJURY RISK IN HEALTHY FEMALES: A SYSTEMATIC REVIEW OF THE LITERATURE.

    Science.gov (United States)

    Dedinsky, Rachel; Baker, Lindsey; Imbus, Samuel; Bowman, Melissa

    2017-01-01

    Background Anterior cruciate ligament (ACL) injury is common among females due to many anatomic, hormonal, and neuromuscular risk factors. One modifiable risk factor that places females at increased risk of ACL injury is a poor hamstrings: quadriceps (H:Q) co-activation ratio, which should be 0.6 or greater in order to decrease the stress placed on the ACL. Exercises that produce more quadriceps dominant muscle activation can add to the tension placed upon the ACL, potentially increasing the risk of ACL injury. Hypothesis/Purpose The purpose of this systematic review was to compare quadriceps and hamstring muscle activation during common closed kinetic chain therapeutic exercises in healthy female knees to determine what exercises are able to produce adequate H:Q co-activation ratios. Study Design Systematic Review Methods Multiple online databases were systematically searched and screened for inclusion. Eight articles were identified for inclusion. Data on mean electromyography (EMG) activation of both quadriceps and hamstring muscles, % maximal voluntary isometric contraction (MVIC), and H:Q co-activation ratios were extracted from the studies. Quality assessment was performed on all included studies. Results Exercises analyzed in the studies included variations of the double leg squat, variations of the single leg squat, lateral step-up, Fitter, Stairmaster® (Core Health and Fitness, Vancouver, WA), and slide board. All exercises, except the squat machine with posterior support at the level of the scapula and feet placed 50 cm in front of the hips, produced higher quadriceps muscle activation compared to hamstring muscle activation. Conclusion Overall, two leg squats demonstrate poor H:Q co-activation ratios. Single leg exercises, when performed between 30 and 90 degrees of knee flexion, produce adequate H:Q ratios, thereby potentially reducing the risk of tensile stress on the ACL and ACL injury. Level of Evidence 2a- Systematic Review of Cohort Studies PMID

  20. Activity test of various mangosteen (Garcinia mangostana pericarp extract fractions to decrease fasting blood cholesterol levels and lipid peroxidation activity in diabetic mice

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    Saikhu Akhmad Husen

    2017-01-01

    Full Text Available The objectives of this study were to determine the effect of various fractions of mangosteen (Garcinia mangostana pericarp extract to the changes of the fasting blood cholesterol and serum malondialdehyde (MDA levels on diabetic mice (Mus musculus. Thirty 3-4 months old male mice strain BALB/c, weight 20-30 g were divided into six groups. The first group was KN as a non diabetic control group, KD as a diabetic control, KM as a group of diabetic mice treated with metformin, and NP, SP, and P as the treatment groups that were treated by using three different fractions from mangosteen pericarp extract, non polar, semi polar, and polar respectively. The induction of Diabetes mellitus was done by the injection of STZ, and the mice were given a high fat diet treatment to induce the hiperlipidemia condition using lard for three weeks. The blood cholesterol levels were measured in all groups before and after the injection of lard, and day 1, 7, and 14 of treatment as well. The serum MDA level as the indicator of lipid peroxidation were measured by using QuantiChrom TBARS Assay Kit (DTBA-100. The data of cholesterol levels were statistically analyzed by t-test, while the data of serum MDA levels were analyzed by variance analysis followed by Duncan test. The results showed that the polar fraction of mangosteen pericarp had effect to decrease the fasting blood cholesterol level in mice, however the non polar and semi polar fraction had no simmilar effect. All of the fractions has shown significant effect to decrease the serum MDA level in mice. Key words: cholesterol, diabetes mellitus, Garcinia mangostana, malondialdehyde (mda, obesity.

  1. Decreased activity of daily living produced by the combination of Alzheimer's disease and lower limb fracture in elderly requiring nursing care.

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    Inagawa, Toshimitsu; Hamagishi, Toshio; Takaso, Yuji; Hitomi, Yoshiaki; Kambayashi, Yasuhiro; Hibino, Yuri; Shibata, Aki; Ngoc, Nguyen T M; Okochi, Jiro; Hatta, Kotaro; Takamuku, Kiyoshi; Konoshita, Tadashi; Nakamura, Hiroyuki

    2013-01-01

    Alzheimer's disease (AD) impairs cognitive functions, subsequently decreasing activity of daily living (ADL), and is frequently accompanied by lower limb fracture including hip fracture in the elderly. However, there have been few studies on what kinds of physical functions are affected or what degrees of dysfunction are produced by this combination. This study aims to clarify the relationship between decreased ADL and the combination of AD and lower limb fracture. We examined present illness and ADL in 4340 elderly aged 82.8 ± 9.36 years [average ± standard deviation (SD)] requiring nursing care and compared ADL between elderly with and without AD or lower limb fracture treated with surgery or conservatively using analysis of covariance (ANCOVA), with age and sex as covariants. We recognized that activities of cognitive function (p lower than in those without the disease, even after adjusting for sex and age. Activities of bed mobility (p fracture treated with surgery were significantly lower, which differed from the results of AD. Significant interactions of AD and fracture treated with surgery on the ADL scores for bed mobility (p fracture alone. We obtained almost the same results for fractures treated conservatively as for fractures treated with surgery. These results demonstrated that the combined effects of AD and lower limb fracture were significantly greater than expected additive effects of AD and fracture, suggesting that the combination of AD and lower limb fracture has synergistic effects on almost all types of ADL except cognitive functions.

  2. Decreased 11β-Hydroxysteroid Dehydrogenase 1 Level and Activity in Murine Pancreatic Islets Caused by Insulin-Like Growth Factor I Overexpression.

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    Subrata Chowdhury

    Full Text Available We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1, which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents to active cortisol (corticosterone in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.

  3. 7-ketocholesterol inhibits Na,K-ATPase activity by decreasing expression of its α1-subunit and membrane fluidity in human endothelial cells.

    Science.gov (United States)

    Duran, M J; Pierre, S V; Lesnik, P; Pieroni, G; Bourdeaux, M; Dignat-Georges, F; Sampol, J; Maixent, J M

    2010-11-09

    As cholesterol, oxysterols, can insert the cell membrane and thereby modify the functions of membrane-bound proteins. The Na,K-ATPase is very sensitive to its lipid environment, seems to be involved in important endothelial functions as the regulation of nitric oxide (NO) release. The effects of 7-ketocholesterol , an oxysterol present in oxidized LDL, was investigated on Na,K-ATPase in isolated human endothelial cells. Cells were incubated 24h with lecithin-, cholesterol- or 7-ketocholesterol liposomes (6 μg/ml). K+-stimulated paranitrophenyl phosphatase activity, reflecting Na,K-ATPase activity, was evaluated as well as cell viability and lipoperoxidation. The expression of Na,K-ATPase subunits mRNAs and membrane fluidity were also investigated. As Na,K-ATPase and nitric oxide seem to be related, we determined the production of NO and the expression of endothelial NO synthase mRNAs. Na,K-ATPase activity was strongly decreased by 7-ketocholesterol. This decrease, not related to lipoperoxidation, was correlated with a decreased expression of the Na,K-ATPase α1-subunit messengers and with rigidity of plasma membranes. Cholesterol induced similar effects but was less potent than 7-ketocholesterol. Basal NO production and expression of endothelial NO synthase mRNAs were not modified by 7-ketocholesterol. Our new findings demonstrate that 7-ketocholesterol, used at non toxic doses, was very potent to disrupt the transport of ions by Na,K-ATPase and perturb membrane structure. These data demonstrate that 7-ketocholesterol induces endothelial dysfunction without cell death that may contribute to early events in atherosclerosis.

  4. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

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    Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  5. Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

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    Young-il Kim

    Full Text Available Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA, which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA, which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.

  6. Oral Administration of the Japanese Traditional Medicine Keishibukuryogan-ka-yokuinin Decreases Reactive Oxygen Metabolites in Rat Plasma: Identification of Chemical Constituents Contributing to Antioxidant Activity

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    Yosuke Matsubara

    2017-02-01

    Full Text Available Insufficient detoxification and/or overproduction of reactive oxygen species (ROS induce cellular and tissue damage, and generated reactive oxygen metabolites become exacerbating factors of dermatitis. Keishibukuryogan-ka-yokuinin (KBGY is a traditional Japanese medicine prescribed to treat dermatitis such as acne vulgaris. Our aim was to verify the antioxidant properties of KBGY, and identify its active constituents by blood pharmacokinetic techniques. Chemical constituents were quantified in extracts of KBGY, crude components, and the plasma of rats treated with a single oral administration of KBGY. Twenty-three KBGY compounds were detected in plasma, including gallic acid, prunasin, paeoniflorin, and azelaic acid, which have been reported to be effective for inflammation. KBGY decreased level of the diacron-reactive oxygen metabolites (d-ROMs in plasma. ROS-scavenging and lipid hydroperoxide (LPO generation assays revealed that gallic acid, 3-O-methylgallic acid, (+-catechin, and lariciresinol possess strong antioxidant activities. Gallic acid was active at a similar concentration to the maximum plasma concentration, therefore, our findings indicate that gallic acid is an important active constituent contributing to the antioxidant effects of KBGY. KBGY and its active constituents may improve redox imbalances induced by oxidative stress as an optional treatment for skin diseases.

  7. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

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    Johanna Abrigo

    2016-01-01

    Full Text Available Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

  8. Activation of immunity, immune response, antioxidant ability, and resistance against Vibrio alginolyticus in white shrimp Litopenaeus vannamei decrease under long-term culture at low pH.

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    Chen, Yu-Yuan; Chen, Jiann-Chu; Tseng, Kuei-Chi; Lin, Yong-Chin; Huang, Chien-Lun

    2015-10-01

    The growth, activation of immunity, immune parameters, and transcript levels of cytMnSOD, mtMnSOD, ecCuZnSOD, glutathione peroxidase (GPx), catalase, lysozyme, and penaeidin 3a were examined in white shrimp Litopenaeus vannamei reared at pH 6.8 and 8.1 after 24 weeks. No significant difference in growth was observed between the two groups. An in vitro study indicated that phenoloxidase activity and respiratory bursts (RB, release of the superoxide anion) were significantly higher in the haemocytes of pH 8.1 shrimp (shrimp reared at pH 8.1) than in pH 6.8 shrimp (shrimp reared at pH 6.8). An in vivo study indicated that the levels of immune parameters of pH 8.1 shrimp were significantly higher than in pH 6.8 shrimp, and the transcript levels of cytMnSOD, ecCuZnSOD, glutathione peroxidase, lysozyme, and penaeidin 3a were down-regulated in pH 6.8 shrimp. In another experiment, shrimp reared at pH 6.8 and 8.1 for 24 weeks were challenged with Vibrio alginolyticus. The mortality rate of pH 6.8 shrimp was significantly higher than in pH 8.1 shrimp over 12-168 h. Phagocytic activity, phagocytic index, and clearance efficiency to V. alginolyticus were significantly lower in pH 6.8 shrimp. We concluded that shrimp under long-term culture at pH 6.8 exhibited decreased resistance against V. alginolyticus as evidenced by reductions in the activation of immunity and immune parameters together with decreased transcript levels of cytMnSOD, ecCuZnSOD, GPx, lysozyme, and penaeidin 3a. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Activation of α7 nicotinic acetylcholine receptor decreases on-site mortality in crush syndrome through insulin signaling-Na/K-ATPase pathway

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    Bo-Shi eFan

    2016-03-01

    Full Text Available On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with anisodamine decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with anisodamine (20 mg/kg and 28 mg/kg respectively, i.p. 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist and PNU282987 (selective α7nAChR agonist, or in α7nAChR knockout mice. Effect of anisodamine was also appraised in C2C12 myotubes. Anisodamine reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by anisodamine. Phosphorylation of Na/K-ATPase was enhanced by anisodamine in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of anisodamine on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway.

  10. Zinc oxide nanoparticles decrease the expression and activity of plasma membrane calcium ATPase, disrupt the intracellular calcium homeostasis in rat retinal ganglion cells.

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    Guo, Dadong; Bi, Hongsheng; Wang, Daoguang; Wu, Qiuxin

    2013-08-01

    Zinc oxide nanoparticle is one of the most important materials with diverse applications. However, it has been reported that zinc oxide nanoparticles are toxic to organisms, and that oxidative stress is often hypothesized to be an important factor in cytotoxicity mediated by zinc oxide nanoparticles. Nevertheless, the mechanism of toxicity of zinc oxide nanoparticles has not been completely understood. In this study, we investigated the cytotoxic effect of zinc oxide nanoparticles and the possible molecular mechanism involved in calcium homeostasis mediated by plasma membrane calcium ATPase in rat retinal ganglion cells. Real-time cell electronic sensing assay showed that zinc oxide nanoparticles could exert cytotoxic effect on rat retinal ganglion cells in a concentration-dependent manner; flow cytometric analysis indicated that zinc oxide nanoparticles could lead to cell damage by inducing the overproduction of reactive oxygen species. Furthermore, zinc oxide nanoparticles could also apparently decrease the expression level and their activity of plasma membrane calcium ATPase, which finally disrupt the intracellular calcium homeostasis and result in cell death. Taken together, zinc oxide nanoparticles could apparently decrease the plasma membrane calcium ATPase expression, inhibit their activity, cause the elevated intracellular calcium ion level and disrupt the intracellular calcium homeostasis. Further, the disrupted calcium homeostasis will trigger mitochondrial dysfunction, generate excessive reactive oxygen species, and finally initiate cell death. Thus, the disrupted calcium homeostasis is involved in the zinc oxide nanoparticle-induced rat retinal ganglion cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Dietary β-conglycinin prevents fatty liver induced by a high-fat diet by a decrease in peroxisome proliferator-activated receptor γ2 protein.

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    Yamazaki, Tomomi; Kishimoto, Kyoko; Miura, Shinji; Ezaki, Osamu

    2012-02-01

    Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). Mice fed a high-fat diet, especially that of saturated-fat-rich oil, develop fatty liver with an increase in peroxisome proliferator-activated receptor (PPAR) γ2 protein in liver. The fatty liver induced by a high-fat diet is improved by knockdown of liver PPARγ2. In this study, we investigated whether β-conglycinin (a major protein of soy protein) could reduce PPARγ2 protein and prevent high-fat-diet-induced fatty liver in ddY mice. Mice were fed a high-starch diet (70 energy% [en%] starch) plus 20% (wt/wt) sucrose in their drinking water or a high-safflower-oil diet (60 en%) or a high-butter diet (60 en%) for 11 weeks, by which fatty liver is developed. As a control, mice were fed a high-starch diet with drinking water. Either β-conglycinin or casein (control) was given as dietary protein. β-Conglycinin supplementation completely prevented fatty liver induced by each type of diet, along with a reduction in adipose tissue weight. β-Conglycinin decreased sterol regulatory element-binding protein (SREBP)-1c and carbohydrate response element-binding protein (ChREBP) messenger RNAs (mRNAs) in sucrose-supplemented mice, whereas it decreased PPARγ2 mRNA (and its target genes CD36 and FSP27), but did not decrease SREBP-1c and ChREBP mRNAs, in mice fed a high-fat diet. β-Conglycinin decreased PPARγ2 protein and liver triglyceride (TG) concentration in a dose-dependent manner in mice fed a high-butter diet; a significant decrease in liver TG concentration was observed at a concentration of 15 en%. In conclusion, β-conglycinin effectively prevents fatty liver induced by a high-fat diet through a decrease in liver PPARγ2 protein. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier K+ current of human atria by inhibiting EGF receptor tyrosine kinase.

    Science.gov (United States)

    Xiao, Guo-Sheng; Zhang, Yan-Hui; Wu, Wei; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

    2017-03-01

    The ultra-rapidly activating delayed rectifier K + current I Kur (encoded by K v 1.5 or KCNA5) plays an important role in human atrial repolarization. The present study investigates the regulation of this current by protein tyrosine kinases (PTKs). Whole-cell patch voltage clamp technique and immunoprecipitation and Western blotting analysis were used to investigate whether the PTK inhibitors genistein, tyrphostin AG556 (AG556) and PP2 regulate human atrial I Kur and hKv1.5 channels stably expressed in HEK 293 cells. Human atrial I Kur was decreased by genistein (a broad-spectrum PTK inhibitor) and AG556 (a highly selective EGFR TK inhibitor) in a concentration-dependent manner. Inhibition of I Kur induced by 30 μM genistein or 10 μM AG556 was significantly reversed by 1 mM orthovanadate (a protein tyrosine phosphatase inhibitor). Similar results were observed in HEK 293 cells stably expressing hK v 1.5 channels. On the other hand, the Src family kinase inhibitor PP2 (1 μM) slightly enhanced I Kur and hK v 1.5 current, and the current increase was also reversed by orthovanadate. Immunoprecipitation and Western blotting analysis showed that genistein, AG556, and PP2 decreased tyrosine phosphorylation of hK v 1.5 channels and that the decrease was countered by orthovanadate. The PTK inhibitors genistein and AG556 decrease human atrial I Kur and cloned hK v 1.5 channels by inhibiting EGFR TK, whereas the Src kinase inhibitor PP2 increases I Kur and hK v 1.5 current. These results imply that EGFR TK and the soluble Src kinases may have opposite effects on human atrial I Kur . © 2017 The British Pharmacological Society.

  13. Five-year decreased incidence of surgical site infections following gastrectomy and prosthetic joint replacement surgery through active surveillance by the Korean Nosocomial Infection Surveillance System.

    Science.gov (United States)

    Choi, H J; Adiyani, L; Sung, J; Choi, J Y; Kim, H B; Kim, Y K; Kwak, Y G; Yoo, H; Lee, Sang-Oh; Han, S H; Kim, S R; Kim, T H; Lee, H M; Chun, H K; Kim, J-S; Yoo, J D; Koo, H-S; Cho, E H; Lee, K W

    2016-08-01

    Surveillance of healthcare-associated infection has been associated with a reduction in surgical site infection (SSI). To evaluate the Korean Nosocomial Infection Surveillance System (KONIS) in order to assess its effects on SSI since it was introduced. SSI data after gastrectomy, total hip arthroplasty (THA), and total knee arthroplasty (TKA) between 2008 and 2012 were analysed. The pooled incidence of SSI was calculated for each year; the same analyses were also conducted from hospitals that had participated in KONIS for at least three consecutive years. Standardized SSI rates for each year were calculated by adjusting for SSI risk factors. SSI trends were analysed using the Cochran-Armitage test. The SSI rate following gastrectomy was 3.12% (522/16,918). There was a significant trend of decreased crude SSI rates over five years. This trend was also evident in analysis of hospitals that had participated for more than three years. The SSI rate for THA was 2.05% (157/7656), which decreased significantly from 2008 to 2012. The risk factors for SSI after THA included the National Nosocomial Infections Surveillance risk index, trauma, reoperation, and age (60-69 years). The SSI rate for TKA was 1.90% (152/7648), which also decreased significantly during a period of five years. However, the risk-adjusted analysis of SSI did not show a significant decrease for all surgical procedures. The SSI incidence of gastrectomy and prosthetic joint replacement declined over five years as a result of active surveillance by KONIS. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  14. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Calon, Frédéric; Lim, Giselle P; Morihara, Takashi; Yang, Fusheng; Ubeda, Oliver; Salem, Norman; Frautschy, Sally A; Cole, Greg M

    2005-08-01

    Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk.

  15. Physical activity decreased by a quarter in the 11- to 12-year-old Swedish boys between 2000 and 2013 but was stable in girls: a smartphone effect?

    Science.gov (United States)

    Raustorp, Anders; Pagels, Peter; Fröberg, Andreas; Boldemann, Cecilia

    2015-08-01

    This study explored physical activity, body mass index (BMI) and overweight and obesity from 2000 to 2013 using a convenience sample of second- and fifth-grade Swedish schoolchildren aged 8-9 years and 11-12 years, respectively. We examined cross-sectional cohorts of 126 second-grade children in 2000, 84 in 2006 and 44 in 2013 and 105 fifth-grade children in 2000 and 38 in 2013. No fifth graders were available in 2006. Physical activity data were collected based on pedometer readings over four consecutive weekdays, and height and weight were measured. Identical instruments and procedures were used in all three years. There was an increase in physical activity in second-grade girls from 2000 to 2006 (p boys and fifth-grade girls were stable throughout the study period. Fifth-grade boys decreased significantly (24%) from 16 670 to 12 704 steps per day (p physical activity differed between boys and girls. Second-grade boys and fifth-grade girls were stable throughout, whereas second-grade girls increased from 2000 to 2006 before stabilising. Fifth-grade boys showed a significant 24% reduction from 2000 to 2013. Changes in recess and leisure time habits, such as smartphone use, may have influenced the result. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  16. Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A₂ in subjects with prediabetes.

    Science.gov (United States)

    Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

    2013-06-01

    Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels prediabetic subjects compared with their controls (p prediabetes (p prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

  17. Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities

    Directory of Open Access Journals (Sweden)

    Jun-Ho Lee

    2015-01-01

    Full Text Available Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW compared with hyperglycemic rats. Here, we elucidated the molecular mechanisms underlying the loss of LW in euglycemic-diabetic rats and identified a potential risk in achieving euglycemia by calorie-control. Sprague-Dawley diabetic rats generated by subtotal-pancreatectomy were fed a calorie-controlled diet for 7 weeks to achieve euglycemia using 19 kcal% (19R or 6 kcal% (6R protein-containing chow or fed ad libitum (19AL. The diet in both R groups was isocaloric/kg body weight to the sham-operated group (19S. Compared with 19S and hyperglycemic 19AL, both euglycemic R groups showed lower LWs, increased autophagy, and increased AMPK and caspase-3 and decreased mTOR activities. Though degree of insulin deficiency was similar among the diabetic rats, Akt activity was lower, and PTEN activity was higher in both R groups than in 19AL whose signaling patterns were similar to 19S. In conclusion, euglycemia achieved by calorie-control is deleterious in insulin deficiency due to increased autophagy and apoptosis in the liver via AMPK and caspase-3 activation.

  18. Bold-functional MRI study of the abnormal cortex and the relationship between the inpairment of vision and the decreased activation of the visual cortex in anisometropic amblyopia

    International Nuclear Information System (INIS)

    Wang Jian; Li Chuanming; Zhou Yang; Xie Bing; Yu Qiongwu; Wang Hui; Qiu Mingguo; Weng Xuchu

    2006-01-01

    . The visual cortical activation increased greatly after refractive correction (Z = -2.197, P=0.028). After refractive correction Brodmann areas 17 was (0.44±0.07) x 10 4 voxels, Brodmann areas 18 and 19 was (3.7±0.3) x 10 4 voxels. While for the fellow sound eyes the activation areas of Brodmann 17 was (0.47±0.07) x 10 4 voxels, and the activation areas of Brodmann 18 and 19 was (3.4±0.4) x 10 4 voxels. The amblyopia eyes were still less than that of the fellow eyes distinctly in all of Brodmannareas 17, 18 and 19(Z=-2.050, -2.524; P=0.040,0.012). In this experiment, all amblyopic eyes have changes on visual acuity and visual cortex activation. The interoculer difference of cortex activation was 0.05±0.04, while the interoculer difference of visual acuity was 0.58±0.22. There was no remarkable linear relationship between them. Conclusion: There are remarkable changes of cortical activation in Brodmann area 17, 18 and 19 on anisometropic amblyopia. Refractive correction can increase amblyopic eye's cortex activation obviously. There is no linear correlation between the decreased cortical activation and visual acuity. This suggests that anisometropic amblyope should be treated as early as possible in the crucial period. (authors)

  19. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

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    Lena Willkomm

    Full Text Available Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs. Lactate (La-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3 known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD vs. high intensity RE (HIT. Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  20. p38 MAPK activation and H3K4 trimethylation is decreased by lactate in vitro and high intensity resistance training in human skeletal muscle.

    Science.gov (United States)

    Willkomm, Lena; Gehlert, Sebastian; Jacko, Daniel; Schiffer, Thorsten; Bloch, Wilhelm

    2017-01-01

    Exercise induces adaptation of skeletal muscle by acutely modulating intracellular signaling, gene expression, protein turnover and myogenic activation of skeletal muscle stem cells (Satellite cells, SCs). Lactate (La)-induced metabolic stimulation alone has been shown to modify SC proliferation and differentiation. Although the mechanistic basis remains elusive, it was demonstrated that La affects signaling via p38 mitogen activated protein kinase (p38 MAPK) which might contribute to trimethylation of histone 3 lysine 4 (H3K4me3) known to regulate satellite cell proliferation and differentiation. We investigated the effects of La on p38 MAPK and H3K4me3 in a model of activated SCs. Differentiating C2C12 myoblasts were treated with La (20 mM) and samples analysed using qRT-PCR, immunofluorescence, and western blotting. We determined a reduction of p38 MAPK phosphorylation, decreased H3K4me3 and reduced expression of Myf5, myogenin, and myosin heavy chain (MHC) leading to decreased differentiation of La-treated C2C12 cells after 5 days of repeated La treatment. We further investigated whether this regulatory pathway would be affected in human skeletal muscle by the application of two different resistance exercise regimes (RE) associated with distinct metabolic demands and blood La accumulation. Muscle biopsies were obtained 15, 30 min, 1, 4, and 24 h post exercise after moderate intensity RE (STD) vs. high intensity RE (HIT). Consistent with in vitro results, reduced p38 phosphorylation and blunted H3K4me3 were also observed upon metabolically demanding HIT RE in human skeletal muscle. Our data provide evidence that La-accumulation acutely affects p38 MAPK signaling, gene expression and thereby cell differentiation and adaptation in vitro, and likely in vivo.

  1. Horizontal infection control strategy decreases methicillin-resistant Staphylococcus aureus infection and eliminates bacteremia in a surgical ICU without active surveillance.

    Science.gov (United States)

    Traa, Maria X; Barboza, Lorena; Doron, Shira; Snydman, David R; Noubary, Farzad; Nasraway, Stanley A

    2014-10-01

    Methicillin-resistant Staphylococcus aureus infection is a significant contributor to morbidity and mortality in hospitalized patients worldwide. Numerous healthcare bodies in Europe and the United States have championed active surveillance per the "search and destroy" model. However, this strategy is associated with significant economic, logistical, and patient costs without any impact on other hospital-acquired pathogens. We evaluated whether horizontal infection control strategies could decrease the prevalence of methicillin-resistant S. aureus infection in the ICU, without the need for active surveillance. Retrospective, observational study in the surgical ICU of a tertiary care medical center in Boston, MA, from 2005 to 2012. A total of 6,697 patients in the surgical ICU. Evidence-based infection prevention strategies were implemented in an iterative fashion, including 1) hand hygiene program with refresher education campaign, 2) chlorhexidine oral hygiene program, 3) chlorhexidine bathing, 4) catheter-associated bloodstream infection program, and 5) daily goals sheets. The prevalence of methicillin-resistant S. aureus infection fell from 2.66 to 0.69 per 1,000 patient days from 2005 to 2012, an average decrease of 21% per year. The biggest decline in rate of infection was detected in 2008, which may suggest that the catheter-associated bloodstream infection prevention program was particularly effective. Among 4,478 surgical ICU admissions over the last 5 years, not a single case of methicillin-resistant S. aureus bacteremia was observed. Aggressive multifaceted horizontal infection control is an effective strategy for reducing the prevalence of methicillin-resistant S. aureus infection and eliminating methicillin-resistant S. aureus bacteremia in the ICU without the need for active surveillance and decontamination.

  2. Decrease in Staphylococcus aureus colonization and hospital-acquired infection in a medical intensive care unit after institution of an active surveillance and decolonization program.

    Science.gov (United States)

    Fraser, Thomas G; Fatica, Cynthia; Scarpelli, Michele; Arroliga, Alejandro C; Guzman, Jorge; Shrestha, Nabin K; Hixson, Eric; Rosenblatt, Miriam; Gordon, Steven M; Procop, Gary W

    2010-08-01

    To evaluate the effects of an active surveillance program for Staphylococcus aureus linked to a decolonization protocol on the incidence of healthcare-associated infection and new nasal colonization due to S. aureus. Retrospective quasi-experimental study. An 18-bed medical intensive care unit at a tertiary care center in Cleveland, Ohio. From January 1, 2006, through December 31, 2007, all patients in the medical intensive care unit were screened for S. aureus nasal carriage at admission and weekly thereafter. During the preintervention period, January 1 through September 30, 2006, only surveillance occurred. During the intervention period, January 1 through December 31, 2007, S. aureus carriers received mupirocin intranasally. Beginning in February 2007, carriers also received chlorhexidine gluconate baths. During the preintervention period, 604 (73.7%) of 819 patients were screened for S. aureus nasal carriage, yielding 248 prevalent carriers (30.3%). During the intervention period, 752 (78.3%) of 960 patients were screened, yielding 276 carriers (28.8%). The incidence of S. aureus carriage decreased from 25 cases in 3,982 patient-days (6.28 cases per 1,000 patient-days) before intervention to 18 cases in 5,415 patient-days (3.32 cases per 1,000 patient-days) (P=.04; relative risk [RR], 0.53 [95% confidence interval {CI}, 0.28-0.97]) and from 9.57 to 4.77 cases per 1,000 at-risk patient-days (P=.02; RR, 0.50 [95% CI, 0.27-0.91]). The incidence of S. aureus hospital-acquired bloodstream infection during the 2 periods was 2.01 and 1.11 cases per 1,000 patient-days, respectively (P=.28). The incidence of S. aureus ventilator-associated pneumonia decreased from 1.51 to 0.18 cases per 1,000 patient-days (P=.03; RR, 0.12 [95% CI, 0.01-0.83]). The total incidence of S. aureus hospital-acquired infection decreased from 3.52 to 1.29 cases per 1,000 patient-days (P=.03; RR, 0.37 [95% CI, 0.14-0.90]). Active surveillance for S. aureus nasal carriage combined with

  3. The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

    International Nuclear Information System (INIS)

    Fossey, Stacey L; London, Cheryl A; Bear, Misty D; Lin, Jiayuh; Li, Chenglong; Schwartz, Eric B; Li, Pui-Kai; Fuchs, James R; Fenger, Joelle; Kisseberth, William C

    2011-01-01

    Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA) cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells. Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT ® ), apoptosis (SensoLyte ® Homogeneous AMC Caspase- 3/7 Assay kit, western blotting), STAT3 DNA binding (EMSA), and vascular endothelial growth factor (VEGF), survivin, and matrix metalloproteinase-2 (MMP2) expression (RT-PCR, western blotting) were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting. Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway. These data demonstrate that the novel curcumin analog FLLL32 has biologic activity

  4. The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines

    Directory of Open Access Journals (Sweden)

    Li Pui-Kai

    2011-03-01

    Full Text Available Abstract Background Curcumin is a naturally occurring phenolic compound shown to have a wide variety of antitumor activities; however, it does not attain sufficient blood levels to do so when ingested. Using structure-based design, a novel compound, FLLL32, was generated from curcumin. FLLL32 possesses superior biochemical properties and more specifically targets STAT3, a transcription factor important in tumor cell survival, proliferation, metastasis, and chemotherapy resistance. In our previous work, we found that several canine and human osteosarcoma (OSA cell lines, but not normal osteoblasts, exhibit constitutive phosphorylation of STAT3. Compared to curcumin, we hypothesized that FLLL32 would be more efficient at inhibiting STAT3 function in OSA cells and that this would result in enhanced downregulation of STAT3 transcriptional targets and subsequent death of OSA cells. Methods Human and canine OSA cells were treated with vehicle, curcumin, or FLLL32 and the effects on proliferation (CyQUANT®, apoptosis (SensoLyte® Homogeneous AMC Caspase- 3/7 Assay kit, western blotting, STAT3 DNA binding (EMSA, and vascular endothelial growth factor (VEGF, survivin, and matrix metalloproteinase-2 (MMP2 expression (RT-PCR, western blotting were measured. STAT3 expression was measured by RT-PCR, qRT- PCR, and western blotting. Results Our data showed that FLLL32 decreased STAT3 DNA binding by EMSA. FLLL32 promoted loss of cell proliferation at lower concentrations than curcumin leading to caspase-3- dependent apoptosis, as evidenced by PARP cleavage and increased caspase 3/7 activity; this could be inhibited by treatment with the pan-caspase inhibitor Z-VAD-FMK. Treatment of OSA cells with FLLL32 decreased expression of survivin, VEGF, and MMP2 at both mRNA and protein levels with concurrent decreases in phosphorylated and total STAT3; this loss of total STAT3 occurred, in part, via the ubiquitin-proteasome pathway. Conclusions These data demonstrate

  5. Blood Mononuclear Cell Mitochondrial Respiratory Chain Complex IV Activity is Decreased in Multiple Sclerosis Patients: Effects of β-Interferon Treatment

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    Iain Hargreaves

    2018-02-01

    Full Text Available Objectives: Evidence of mitochondrial respiratory chain (MRC dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS. However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment. Methods: Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls. Results: MRC Complex IV activity was found to be significantly decreased (p < 0.05 in MS patients (2.1 ± 0.8 k/nmol × 10−3; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10−3. Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10−3 was not found to be significantly different from that of the controls. Conclusions: This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s of action of β-interferon.

  6. Tranexamic acid suppresses ultraviolet B eye irradiation-induced melanocyte activation by decreasing the levels of prohormone convertase 2 and alpha-melanocyte-stimulating hormone.

    Science.gov (United States)

    Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

    2014-12-01

    Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Neurogenic detrusor overactivity is associated with decreased expression and function of the large conductance voltage- and Ca(2+-activated K(+ channels.

    Directory of Open Access Journals (Sweden)

    Kiril L Hristov

    Full Text Available Patients suffering from a variety of neurological diseases such as spinal cord injury, Parkinson's disease, and multiple sclerosis often develop neurogenic detrusor overactivity (NDO, which currently lacks a universally effective therapy. Here, we tested the hypothesis that NDO is associated with changes in detrusor smooth muscle (DSM large conductance Ca(2+-activated K(+ (BK channel expression and function. DSM tissue samples from 33 patients were obtained during open bladder surgeries. NDO patients were clinically characterized preoperatively with pressure-flow urodynamics demonstrating detrusor overactivity, in the setting of a clinically relevant neurological condition. Control patients did not have overactive bladder and did not have a clinically relevant neurological disease. We conducted quantitative polymerase chain reactions (qPCR, perforated patch-clamp electrophysiology on freshly-isolated DSM cells, and functional studies on DSM contractility. qPCR experiments revealed that DSM samples from NDO patients showed decreased BK channel mRNA expression in comparison to controls. Patch-clamp experiments demonstrated reduced whole cell and transient BK currents (TBKCs in freshly-isolated DSM cells from NDO patients. Functional studies on DSM contractility showed that spontaneous phasic contractions had a decreased sensitivity to iberiotoxin, a selective BK channel inhibitor, in DSM strips isolated from NDO patients. These results reveal the novel finding that NDO is associated with decreased DSM BK channel expression and function leading to increased DSM excitability and contractility. BK channel openers or BK channel gene transfer could be an alternative strategy to control NDO. Future clinical trials are needed to evaluate the value of BK channel opening drugs or gene therapies for NDO treatment and to identify any possible adverse effects.

  8. Actinomycin D synergistically enhances the cytotoxicity of CDDP on KB cells by activating P53 via decreasing P53-MDM2 complex.

    Science.gov (United States)

    Wang, Lin; Pang, Xiao-Cong; Yu, Zi-Ru; Yang, Sheng-Qian; Liu, Ai-Lin; Wang, Jin-Hua; Du, Guan-Hua

    2017-06-01

    The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX was analyzed by Discovery Studio. The content of P53-MDM2 complex was detected by ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD in kinds of cancer cells. Molecular docking showed strong interaction between ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53-MDM2 complex. Significant increase of the apoptotic activity by the combination therapy in KB cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells. The reactivation of P53 was probably achieved by disturbing the interaction of P53 and MDM2/MDMX.

  9. Reversal of diabetic peripheral neuropathy with phototherapy (MIRE) decreases falls and the fear of falling and improves activities of daily living in seniors.

    Science.gov (United States)

    Powell, Mark W; Carnegie, Dale H; Burke, Thomas J

    2006-01-01

    to determine whether restoration of sensation, impaired due to diabetic peripheral neuropathy (DPN), would reduce the number of falls and the fear of falling and improve activities of daily living (ADL) in a Medicare-aged population. retrospective cohort study of patients with documented, monochromatic near-infrared phototherapy (MIRE)-mediated, symptomatic reversal of DPN. responses to a health status questionnaire following symptomatic reversal of DPN. 252 patients (mean age 76 years) provided health information following symptomatic reversal of diabetic neuropathy (mean duration 8.6 months). incidence of falls and fear of falling decreased within 1 month after reversal of peripheral neuropathy and remained low after 1 year. Likewise, improved ADL were evident soon after reversal of peripheral neuropathy and showed further improvement after 1 year. Overall, reversal of peripheral neuropathy in a clinician's office and subsequent use of MIRE at home was associated with a 78% reduction in falls, a 79% decrease in balance-related fear of falling and a 72% increase in ADL (P < 0.0002 for all results). reversal of peripheral neuropathy is associated with an immediate reduction in the absolute number of falls, a reduced fear of falling and improved ADL. These results suggest that symptomatic reversal of diabetic neuropathy will have a substantial favourable, long-term socioeconomic impact on patients with DPN and the Medicare system, and improve the quality of life for elderly patients with diabetes and peripheral neuropathy.

  10. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviors in aged mice.

    Science.gov (United States)

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2017-06-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation, and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here they show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviors. Using both Grhl3-knockout mice (Grhl3 -/- ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3 flox/flox ), they performed histological expression analyses and behavioral tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety, and stress. They found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain; however, aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviors suggestive of decreased fear and anxiety. They conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behavior or hyperactivity. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 775-788, 2017. © 2017 Wiley Periodicals, Inc.

  11. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Haupt, Thomas Huneck; Andersen, Aino L

    2017-01-01

    inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet...... (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator...... receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P...

  12. Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

    2014-01-01

    Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

  13. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells

    Science.gov (United States)

    Li, Luyuan; Paz, Ana C.; Wilky, Breelyn A.; Johnson, Britt; Galoian, Karina; Rosenberg, Andrew; Hu, Guozhi; Tinoco, Gabriel; Bodamer, Olaf; Trent, Jonathan C.

    2015-01-01

    Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG) in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas. PMID:26368816

  14. Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells.

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    Luyuan Li

    Full Text Available Chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2 were recently described in several cancers including chondrosarcomas. The IDH1 inhibitor AGI-5198 abrogates the ability of mutant IDH1 to produce the oncometabolite D-2 hydroxyglutarate (D-2HG in gliomas. We sought to determine if treatment with AGI-5198 would similarly inhibit tumorigenic activity and D-2HG production in IDH1-mutant human chondrosarcoma cells. Two human chondrosarcoma cell lines, JJ012 and HT1080 with endogenous IDH1 mutations and a human chondrocyte cell line C28 with wild type IDH1 were employed in our study. Mutation analysis of IDH was performed by PCR-based DNA sequencing, and D-2HG was detected using tandem mass spectrometry. We confirmed that JJ012 and HT1080 harbor IDH1 R132G and R132C mutation, respectively, while C28 has no mutation. D-2HG was detectable in cell pellets and media of JJ012 and HT1080 cells, as well as plasma and urine from an IDH-mutant chondrosarcoma patient, which decreased after tumor resection. AGI-5198 treatment decreased D-2HG levels in JJ012 and HT1080 cells in a dose-dependent manner, and dramatically inhibited colony formation and migration, interrupted cell cycling, and induced apoptosis. In conclusion, our study demonstrates anti-tumor activity of a mutant IDH1 inhibitor in human chondrosarcoma cell lines, and suggests that D-2HG is a potential biomarker for IDH mutations in chondrosarcoma cells. Thus, clinical trials of mutant IDH inhibitors are warranted for patients with IDH-mutant chondrosarcomas.

  15. Hypomethylation mediated by decreased DNMTs involves in the activation of proto-oncogene MPL in TK6 cells treated with hydroquinone.

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    Liu, Linhua; Ling, Xiaoxuan; Liang, Hairong; Gao, Yuting; Yang, Hui; Shao, Junli; Tang, Huanwen

    2012-03-25

    Hydroquinone (HQ), one of the most important metabolites derived from benzene, is known to be associated with acute myelogenous leukemia (AML) risk, however, its carcinogenic mechanism remains unclear. In this study, the epigenetic mechanism of HQ exposure was investigated. We characterized the epigenomic response of TK6 cells to HQ exposure, and examined the mRNA expression of DNA methyltransferases (DNMTs) including DNMT1, DNMT3a and DNMT3b, methyl-CpG-binding domain protein 2 (MBD2) and six proto-oncogenes (MPL, RAF1, MYB, MYC, ERBB2 and BRAF). Compared to the control cells, HQ exposure (2.5, 5.0, 10.0 and 20.0 μM for 48 h) resulted in the decrease of DNMTs and MBD2 expression, the global hypomethylation and increase of MPL at mRNA level. Meanwhile, most of these changes were in dose-dependent manner. Moreover, inhibition of DNMTs induced by 5-aza-2'-deoxycytidine (5-AZA), an identified DNMT inhibitor, caused more induction of MPL expression at mRNA level compared to the HQ (10.0 μM) pre-treated group. Furthermore, treatment of HQ potentially led to MPL itself hypomethylation (10.0 and 20.0 μM reduced by 47% and 44%, respectively), further revealing that the activation of proto-oncogene MPL was related to hypomethylation in its DNA sequences. In conclusion, hypomethylation, including global and specific hypomethylation, might be involved in the activation of MPL, and the hypomethylation could be induced by decreased DNMTs in TK6 cells exposed to HQ. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. High-intensity physical activity, stable relationship, and high education level associate with decreasing risk of erectile dysfunction in 1,000 apparently healthy cardiovascular risk subjects.

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    Ettala, Otto O; Syvänen, Kari T; Korhonen, Päivi E; Kaipia, Antti J; Vahlberg, Tero J; Boström, Peter J; Aarnio, Pertti T

    2014-09-01

    Erectile dysfunction (ED) is especially common in men with cardiovascular diseases (CVDs). However, the data are scarce concerning populations without manifested CVD. The aim of this study was to describe factors associated with ED, especially those associated with decreasing risk of ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic renal disease. In 2004 to 2007, a cross-sectional population-based sample of men 45 to 70 years old in two rural towns in Finland was collected. Men with previously diagnosed CVD, diabetes, or kidney disease were not invited to the study. In total 1,000 eligible men with cardiovascular risk factors, i.e., central obesity, high scores in the Finnish Diabetes Risk Score, high blood pressure, antihypertensive medication, or family history of coronary heart disease, myocardial infarction, or stroke, were included in the analysis. Questionnaires, clinical measurements, and laboratory tests were obtained. The prevalence of ED was studied comparing the means, and risk factors were studied using multivariate logistic regression analysis. The rate of ED was defined by the International Index of Erectile Function short form (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain an erection. The prevalence of ED was 57% or 68% using IIEF-5 or 2Q, respectively. Age (odds ratio [OR]: up to 9.16; 95% confidence interval [CI], 5.00-16.79; P physical activity (OR: 0.50; 95% CI, 0.29-0.86; P = 0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable relationship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED. In apparently healthy men with cardiovascular risk factors, decreasing risk of ED is associated with high-intensity physical activity, stable relationship, and high education level. © 2014 International Society for Sexual Medicine.

  17. An altered gp100 peptide ligand with decreased binding by TCR and CD8alpha dissects T cell cytotoxicity from production of cytokines and activation of NFAT

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    Niels eSchaft

    2013-09-01

    Full Text Available Altered peptide ligands (APLs provide useful tools to study T cell activation and potentially direct immune responses to improve treatment of cancer patients. To better understand and exploit APLs, we studied the relationship between APLs and T cell function in more detail. Here, we tested a broad panel of gp100(280-288 APLs with respect to T cell cytotoxicity, production of cytokines and activation of Nuclear Factor of Activated T cells (NFAT by human T cells gene-engineered with a gp100-HLA-A2-specific TCRalpha/beta. We demonstrated that gp100-specific cytotoxicity, production of cytokines, and activation of NFAT were not affected by APLs with single amino acid substitutions, except for an APL with an amino acid substitution at position 3 (APL A3, which did not elicit any T cell response. A gp100 peptide with a double amino acid mutation (APL S4S6 elicited T cell cytotoxicity and production of IFNgamma, and to a lesser extent TNFalpha, IL-4, and IL-5, but not production of IL-2 and IL-10, or activation of NFAT. Notably, TCR-mediated functions showed decreases in sensitivities for S4S6 versus gp100 wt peptide, which were minor for cytotoxicity but at least a 1000-fold more prominent for the production of cytokines. TCR-engineered T cells did not bind A3-HLA-A2, but did bind S4S6-HLA-A2 although to a lowered extent compared to wt peptide-HLA-A2. Moreover, S4S6-induced T cell function demonstrated an enhanced dependency on CD8alpha. Taken together, most gp100 APLs functioned as agonists, but A3 and S4S6 peptides acted as a null ligand and partial agonist, respectively. Our results further suggest that TCR-mediated cytotoxicity can be dissected from production of cytokines and activation of NFAT, and that the agonist potential of peptide mutants relates to the extent of binding by TCR and CD8alpha. These findings may facilitate the design of APLs to advance the study of T cell activation and their use for therapeutic applications.

  18. Increased tumour ascorbate is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer

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    Caroline eKuiper

    2014-02-01

    Full Text Available Ascorbate is a co-factor for the hydroxylases that regulate the transcription factor hypoxia-inducible factor (HIF-1, which provides cancer cells with a metabolic and survival advantage in the hypoxic environment of solid tumors. However, whether ascorbate affects tumor development is a highly debated issue. We aimed to determine whether tumor ascorbate was associated with HIF-1 activation and patient disease-free survival. In this study we undertook a retrospective observational analysis of tissue-banked tumor and paired normal tissue from 49 colorectal cancer patients, measuring ascorbate levels, HIF-1α and its downstream gene products BNIP3 and VEGF. Patient survival was monitored for the first six years after surgery. We found that ascorbate levels were lower in tumor tissue compared to normal tissue (p< 0.001 but overall levels varied considerably. HIF-1α, VEGF and BNIP3 were elevated in tumor samples (p< 0.01. There was an inverse relationship between tumor ascorbate content and HIF-1 pathway activation (p=0.002 and tumor size (p=0.018. Higher tumor ascorbate content was associated with significantly improved disease-free survival in the first 6 years after surgery (p=0.006, with 141 - 1,094 additional disease free days. This was independent of tumor grade and stage. Survival advantage was associated with the amount of ascorbate in the tumor, but not with the amount in adjacent normal tissue. Our results demonstrate that higher tumor ascorbate content is associated decreased HIF-1 activation, most likely due to the co-factor activity of ascorbate for the regulatory HIF hydroxylases. Our findings support the need for future studies to determine whether raising tumor ascorbate is possible with clinical intervention and whether this results in modification of hydroxylase-dependent pathways in the tumor.

  19. Rationale, design and methods for a randomised and controlled trial to investigate whether home access to electronic games decreases children's physical activity

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    Piek Jan P

    2009-06-01

    Full Text Available Abstract Background Many children are reported to have insufficient physical activity (PA placing them at greater risk of poor health outcomes. Participating in sedentary activities such as playing electronic games is widely believed to contribute to less PA. However there is no experimental evidence that playing electronic games reduces PA. There is also no evidence regarding the effect of different types of electronic games (traditional sedentary electronic games versus new active input electronic games on PA. Further, there is a poor understanding about how characteristics of children may moderate the impact of electronic game access on PA and about what leisure activities are displaced when children play electronic games. Given that many children play electronic games, a better understanding of the effect of electronic game use on PA is critical to inform child health policy and intervention. Methods This randomised and controlled trial will examine whether PA is decreased by access to electronic games and whether any effect is dependent on the type of game input or the child's characteristics. Children aged 10–12 years (N = 72, 36 females will be recruited and randomised to a balanced ordering of 'no electronic games', 'traditional' electronic games and 'active' electronic games. Each child will participate in each condition for 8 weeks, and be assessed prior to participation and at the end of each condition. The primary outcome is PA, assessed by Actical accelerometers worn for 7 days on the wrist and hip. Energy expenditure will be assessed by the doubly labelled water technique and motor coordination, adiposity, self-confidence, attitudes to technology and PA and leisure activities will also be assessed. A sample of 72 will provide a power of > 0.9 for detecting a 15 mins difference in PA (sd = 30 mins. Discussion This is the first such trial and will provide critical information to understand whether access to electronic games affects

  20. Buddleja globosa (matico) prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling.

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    Fuentes, Manuel; Sepúlveda, Cesar; Alarcón, Marcelo; Palomo, Iván; Fuentes, Eduardo

    2018-01-01

    Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as "matico") is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC 50 values was 61 μg/mL, 72 μg/mL and 290 μg/mL, respectively). In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05), 19 ± 1 (p < 0.01), 15 ± 2 (p < 0.01), 10 ± 1% (p < 0.01) and 7 ± 2% (p < 0.01), respectively) and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s), 55 ± 2 (p < 0.05), 50 ± 2 (p < 0.01), 38 ± 1 (p < 0.01), 36 ± 2 (p < 0.01). The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

  1. Buddleja globosa (matico prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling

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    Manuel Fuentes

    2018-01-01

    Full Text Available Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as “matico” is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05–1 mg/mL was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC50 values was 61 μg/mL, 72 μg/mL and 290 μg/mL, respectively. In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05, 19 ± 1 (p < 0.01, 15 ± 2 (p < 0.01, 10 ± 1% (p < 0.01 and 7 ± 2% (p < 0.01, respectively and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s, 55 ± 2 (p < 0.05, 50 ± 2 (p < 0.01, 38 ± 1 (p < 0.01, 36 ± 2 (p < 0.01. The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

  2. Release from Xenopus oocyte prophase I meiotic arrest is independent of a decrease in cAMP levels or PKA activity.

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    Nader, Nancy; Courjaret, Raphael; Dib, Maya; Kulkarni, Rashmi P; Machaca, Khaled

    2016-06-01

    Vertebrate oocytes arrest at prophase of meiosis I as a result of high levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity. In Xenopus, progesterone is believed to release meiotic arrest by inhibiting adenylate cyclase, lowering cAMP levels and repressing PKA. However, the exact timing and extent of the cAMP decrease is unclear, with conflicting reports in the literature. Using various in vivo reporters for cAMP and PKA at the single-cell level in real time, we fail to detect any significant changes in cAMP or PKA in response to progesterone. More interestingly, there was no correlation between the levels of PKA inhibition and the release of meiotic arrest. Furthermore, we devised conditions whereby meiotic arrest could be released in the presence of sustained high levels of cAMP. Consistently, lowering endogenous cAMP levels by >65% for prolonged time periods failed to induce spontaneous maturation. These results argue that the release of oocyte meiotic arrest in Xenopus is independent of a reduction in either cAMP levels or PKA activity, but rather proceeds through a parallel cAMP/PKA-independent pathway. © 2016. Published by The Company of Biologists Ltd.

  3. Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs.

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    Chen, Zhe; Chen, Hui; Chen, Fagui; Gu, Dachuan; Sun, Lejia; Zhang, Weitao; Fan, Linfeng; Lin, Yong; Dong, Rong; Lai, Kefang

    2017-12-20

    Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

  4. Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age‐related declines in voluntary physical activity

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    Ruegsegger, Gregory N.; Toedebusch, Ryan G.; Childs, Thomas E.; Grigsby, Kolter B.

    2016-01-01

    Key points Physical inactivity, which drastically increases with advancing age, is associated with numerous chronic diseases.The nucleus accumbens (the pleasure and reward ‘hub’ in the brain) influences wheel running behaviour in rodents.RNA‐sequencing and subsequent bioinformatics analysis led us to hypothesize a potential relationship between the regulation of dendritic spine density, the molecules involved in synaptic transmission, and age‐related reductions in wheel running. Upon completion of follow‐up studies, we developed the working model that synaptic plasticity in the nucleus accumbens is central to age‐related changes in voluntary running.Testing this hypothesis, inhibition of Cdk5 (comprising a molecule central to the processes described above) in the nucleus accumbens reduced wheel running.The results of the present study show that reductions in synaptic transmission and Cdk5 function are related to decreases in voluntary running behaviour and provide guidance for understanding the neural mechanisms that underlie age‐dependent reductions in the motivation to be physically active. Abstract Increases in age are often associated with reduced levels of physical activity, which, in turn, associates with the development of numerous chronic diseases. We aimed to assess molecular differences in the nucleus accumbens (NAc) (a specific brain nucleus postulated to influence rewarding behaviour) with respect to wheel running and sedentary female Wistar rats at 8 and 14 weeks of age. RNA‐sequencing was used to interrogate transcriptomic changes between 8‐ and 14‐week‐old wheel running rats, and select transcripts were later analysed by quantitative RT‐PCR in age‐matched sedentary rats. Voluntary wheel running was greatest at 8 weeks and had significantly decreased by 12 weeks. From 619 differentially expressed mRNAs, bioinformatics suggested that cAMP‐mediated signalling, dopamine‐ and cAMP‐regulated neuronal phosphoprotein of 32

  5. Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

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    Julie Sahler

    Full Text Available Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ. In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles

  6. Microparticles engineered to highly express peroxisome proliferator-activated receptor-γ decreased inflammatory mediator production and increased adhesion of recipient monocytes.

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    Sahler, Julie; Woeller, Collynn F; Phipps, Richard P

    2014-01-01

    Circulating blood microparticles are submicron vesicles released primarily by megakaryocytes and platelets that act as transcellular communicators. Inflammatory conditions exhibit elevated blood microparticle numbers compared to healthy conditions. Direct functional consequences of microparticle composition, especially internal composition, on recipient cells are poorly understood. Our objective was to evaluate if microparticle composition could impact the function of recipient cells, particularly during inflammatory provocation. We therefore engineered the composition of megakaryocyte culture-derived microparticles to generate distinct microparticle populations that were given to human monocytes to assay for influences recipient cell function. Herein, we tested the responses of monocytes exposed to either control microparticles or microparticles that contain the anti-inflammatory transcription factor, peroxisome proliferator-activated receptor-γ (PPARγ). In order to normalize relative microparticle abundance from two microparticle populations, we implemented a novel approach that utilizes a Nanodrop Spectrophotometer to assay for microparticle density rather than concentration. We found that when given to peripheral blood mononuclear cells, microparticles were preferentially internalized by CD11b+ cells, and furthermore, microparticle composition had a profound functional impact on recipient monocytes. Specifically, microparticles containing PPARγ reduced activated monocyte production of the proinflammatory cytokines interleukin-8 and monocyte chemotactic protein-1 compared to activated monocytes exposed to control microparticles. Additionally, treatment with PPARγ microparticles greatly increased monocyte cell adherence. This change in morphology occurred simultaneously with increased production of the key extracellular matrix protein, fibronectin and increased expression of the fibronectin-binding integrin, ITGA5. PPARγ microparticles also changed monocyte

  7. Deep tissue injury in development of pressure ulcers: a decrease of inflammasome activation and changes in human skin morphology in response to aging and mechanical load.

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    Olivera Stojadinovic

    Full Text Available Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load of 300 kPa (determined by pressure plate analyses of a person in a reclining position for 0.5-4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers.

  8. Stroke promotes survival of nearby transplanted neural stem cells by decreasing their activation of caspase 3 while not affecting their differentiation.

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    Kosi, Nina; Alić, Ivan; Salamon, Iva; Mitrečić, Dinko

    2018-02-14

    Although transplantation of stem cells improves recovery of the nervous tissue, little is known about the influence of different brain regions on transplanted cells. After we confirmed that cells with uniform differentiation potential can be generated in independent experiments, one million of neural stem cells isolated from B6.Cg-Tg(Thy1-YFP)16Jrs/J mouse embryos were transplanted into the brain 24 h after induction of stroke. The lateral ventricles, the corpus callosum and the striatum were tested. Two and four weeks after the transplantation, the cells transplanted in all three regions have been attracted to the ischemic core. The largest number of attracted cells has been observed after transplantation into the striatum. Their differentiation pattern and expression of neuroligin 1, SynCAM 1, postsynaptic density protein 95 and synapsin 1 followed the same pattern observed during in vitro cultivation and it did not differ among the tested regions. Differentiation pattern of the cells transplanted in the stroke-affected and healthy animals was the same. On the other hand, neural stem cells transplanted in the striatum of the animals affected by stroke exhibited significantly increased survival rates reaching 260 ± 19%, when compared to cells transplanted in their wild type controls. Surprisingly, improved survival two and four weeks after transplantation was not due to increased proliferation of the grafted cells and it was accompanied by decreased levels of activity of Casp3 (19.56 ± 3.1% in the stroke-affected vs. 30.14 ± 2.4% in healthy animals after four weeks). We assume that the decreased levels of Casp3 in cells transplanted near the ischemic region was linked to increased vasculogenesis, synaptogenesis, astrocytosis and axonogenesis detected in the host tissue affected by ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Continuous high and low temperature induced a decrease of photosynthetic activity and changes in the diurnal fluctuations of organic acids in Opuntia streptacantha.

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    Zaida Zarely Ojeda-Pérez

    Full Text Available Opuntia plants grow naturally in areas where temperatures are extreme and highly variable in the day during the entire year. These plants survive through different adaptations to respond to adverse environmental conditions. Despite this capability, it is unknown how CAM photosynthetic activity and growth in Opuntia plantlets is affected by constant heat or cold. Therefore, the main objective of this research was to evaluate the short-term effect of high (40°C and low (4°C continuous temperatures on the photosynthetic efficiency, the organic acid content (malic acid and the relative growth rate (RGR in seven-month-old Opuntia streptacantha plantlets during 5, 10, and 15 days. Chlorophyll fluorescence analysis allowed us to determine that high temperatures negatively impact the photosynthetic efficiency of O. streptacantha plantlets, which exhibited the lowest values of maximum quantum efficiency of the photosystem II (Fv/Fm = 52%, Fv/F0 = 85%, operational quantum yield of PS (ΦPSII = 65% and relative electron transport rate (rETR = 65%, as well as highest values of basal fluorescence (F0 = 226% during 15 days of treatment. Similarly, low temperatures decreased Fv/Fm (16%, Fv/F0 (50%, ΦPSII and rETR (16%. High temperatures also decreased nocturnal acidification in approximately 34-50%, whereas low temperatures increased it by 30-36%. Additionally, both continuous temperatures affected drastically diurnal consumption of malic acid, which was related to a significant RGR inhibition, where the specific photosynthetic structure area component was the most affected. Our results allowed determining that, despite the high tolerance to extreme temperatures described for Opuntia plants, young individuals of O. streptacantha suffered photosynthetic impairment that led to the inhibition of their growth. Thus, the main findings reported in this study can help to predict the potential impact of climatic change on the establishment and survival of succulent

  10. Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR

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    Van Calenbergh Serge

    2008-09-01

    Full Text Available Abstract Background To date, only few compounds targeting the AI-2 based quorum sensing (QS system are known. In the present study, we screened cinnamaldehyde and substituted cinnamaldehydes for their ability to interfere with AI-2 based QS. The mechanism of QS inhibition was elucidated by measuring the effect on bioluminescence in several Vibrio harveyi mutants. We also studied in vitro the ability of these compounds to interfere with biofilm formation, stress response and virulence of Vibrio spp. The compounds were also evaluated in an in vivo assay measuring the reduction of Vibrio harveyi virulence towards Artemia shrimp. Results Our results indicate that cinnamaldehyde and several substituted derivatives interfere with AI-2 based QS without inhibiting bacterial growth. The active compounds neither interfered with the bioluminescence system as such, nor with the production of AI-2. Study of the effect in various mutants suggested that the target protein is LuxR. Mobility shift assays revealed a decreased DNA-binding ability of LuxR. The compounds were further shown to (i inhibit biofilm formation in several Vibrio spp., (ii result in a reduced ability to survive starvation and antibiotic treatment, (iii reduce pigment and protease production in Vibrio anguillarum and (iv protect gnotobiotic Artemia shrimp against virulent Vibrio harveyi BB120. Conclusion Cinnamaldehyde and cinnamaldehyde derivatives interfere with AI-2 based QS in various Vibrio spp. by decreasing the DNA-binding ability of LuxR. The use of these compounds resulted in several marked phenotypic changes, including reduced virulence and increased susceptibility to stress. Since inhibitors of AI-2 based quorum sensing are rare, and considering the role of AI-2 in several processes these compounds may be useful leads towards antipathogenic drugs.

  11. Cinnamaldehyde and cinnamaldehyde derivatives reduce virulence in Vibrio spp. by decreasing the DNA-binding activity of the quorum sensing response regulator LuxR

    Science.gov (United States)

    Brackman, Gilles; Defoirdt, Tom; Miyamoto, Carol; Bossier, Peter; Van Calenbergh, Serge; Nelis, Hans; Coenye, Tom

    2008-01-01

    Background To date, only few compounds targeting the AI-2 based quorum sensing (QS) system are known. In the present study, we screened cinnamaldehyde and substituted cinnamaldehydes for their ability to interfere with AI-2 based QS. The mechanism of QS inhibition was elucidated by measuring the effect on bioluminescence in several Vibrio harveyi mutants. We also studied in vitro the ability of these compounds to interfere with biofilm formation, stress response and virulence of Vibrio spp. The compounds were also evaluated in an in vivo assay measuring the reduction of Vibrio harveyi virulence towards Artemia shrimp. Results Our results indicate that cinnamaldehyde and several substituted derivatives interfere with AI-2 based QS without inhibiting bacterial growth. The active compounds neither interfered with the bioluminescence system as such, nor with the production of AI-2. Study of the effect in various mutants suggested that the target protein is LuxR. Mobility shift assays revealed a decreased DNA-binding ability of LuxR. The compounds were further shown to (i) inhibit biofilm formation in several Vibrio spp., (ii) result in a reduced ability to survive starvation and antibiotic treatment, (iii) reduce pigment and protease production in Vibrio anguillarum and (iv) protect gnotobiotic Artemia shrimp against virulent Vibrio harveyi BB120. Conclusion Cinnamaldehyde and cinnamaldehyde derivatives interfere with AI-2 based QS in various Vibrio spp. by decreasing the DNA-binding ability of LuxR. The use of these compounds resulted in several marked phenotypic changes, including reduced virulence and increased susceptibility to stress. Since inhibitors of AI-2 based quorum sensing are rare, and considering the role of AI-2 in several processes these compounds may be useful leads towards antipathogenic drugs. PMID:18793453

  12. Response to platelet-activating factor in human platelets stored and aged in plasma. Decrease in aggregation, phosphoinositide turnover, and receptor affinity

    International Nuclear Information System (INIS)

    Shukla, S.D.; Morrison, W.J.; Klachko, D.M.

    1989-01-01

    Human platelet concentrates were stored in polyolefin bags at 22 to 24 degrees C on a horizontal shaker for up to 8 days. At different intervals, aliquots of platelet-rich plasma (PRP) were removed aseptically and five variables, i.e., platelet counts, morphology, platelet-activating factor (PAF)-stimulated aggregation, phosphoinositide turnover, and [3H]PAF binding to platelet receptors, were studied. The number of platelets did not change during the 8 days of storage. Scanning electron microscopy of the platelets revealed a gradual morphologic change from biconcave flat discs to irregular, crenated forms. The PAF-induced aggregation of platelets declined with time of storage. A decrease to 50 percent of the Day 1 aggregatory response to PAF was evident on Day 2, and there was a further decline to about 20 percent by Day 6. Similarly, PAF receptor-coupled phosphoinositide turnover, as monitored by 32P incorporation into individual phosphoinositides, decreased dramatically with storage. After 2 to 3 days of storage, the phosphoinositide turnover was reduced to 50 percent of the original response, and it continued to decline to about 25 percent of original response by Day 5 or 6. The binding of [3H]PAF to washed human platelets indicated subtle changes between Days 2 and 4, which became more noticeable by Day 6. These results have raised the possibility of changes in the number of the receptors and/or their affinity for the ligand during storage. We conclude that although the number of platelets was maintained during storage for 8 days, a general deterioration of their responses to PAF occurred at the levels of cell surface receptor, transmembrane signaling (phosphoinositide turnover), and response (aggregation)

  13. Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage.

    Directory of Open Access Journals (Sweden)

    Isobel J Whitehouse

    Full Text Available The cellular prion protein (PrP(C has been implicated in the development of Alzheimer's disease (AD. PrP(C decreases amyloid-β (Aβ production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1 activity. Contactin 5 (CNTN5 has also been implicated in the development of AD by a genome-wide association study. Here we measured PrP(C and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrP(C was decreased in sporadic AD compared to controls (by 49%, p = 0.014 but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217. PrP(C significantly inversely correlated with BACE1 activity (rs = -0.358, p = 0.006, Aβ load (rs = -0.456, p = 0.001, soluble Aβ (rs = -0.283, p = 0.026 and insoluble Aβ (rs = -0.353, p = 0.007 and PrP(C also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (rs = -0.377, p = 0.007. CNTN5 did not correlate with Aβ load (rs = 0.040, p = 0.393, soluble Aβ (rs = 0.113, p = 0.223 or insoluble Aβ (rs = 0.169, p = 0.125. PrP(C was also measured in frontal cortex samples from 9 Down's syndrome (DS and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrP(C in the DS brains compared to controls (p = 0.625. These data are consistent with a role for PrP(C in regulating Aβ production and indicate that brain PrP(C level may be important in influencing the onset and progression of sporadic AD.

  14. Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

    Directory of Open Access Journals (Sweden)

    Dexter L. Lee

    2011-01-01

    Full Text Available Peroxisome proliferator-activated receptor-alpha (PPAR-α activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin-6 (IL-6. Fenofibrate also induces cytochrome P450 4A (CYP4A and increases 20-hydroxyeicosatetraenoic acid (20-HETE production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2, while increasing expression of renal CYP4A during 7 days of DOCA-salt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5 mg/g treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically. Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23 and soluble expoxide hydrolase (sEH expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.

  15. Gadolinium released by the linear gadolinium-based contrast-agent Gd-DTPA decreases the activity of human epithelial Na+ channels (ENaCs).

    Science.gov (United States)

    Knoepp, Fenja; Bettmer, Joerg; Fronius, Martin

    2017-05-01

    Gadolinium-based-contrast-agents (GBCAs) are used for magnetic-resonance-imaging and associated with renal and cardiovascular adverse reactions caused by released Gd 3+ ions. Gd 3+ is also a modulator of mechano-gated ion channels, including the epithelial Na + channel (ENaC) that is expressed in kidney epithelium and the vasculature. ENaC is important for salt-/water homeostasis and blood pressure regulation and a likely target of released Gd 3+ from GBCAs causing the above-mentioned adverse reactions. Therefore this study examined the effect of Gd 3+ and GBCAs on ENaC's activity. Human αβγENaC was expressed in Xenopus laevis oocytes and exposed to Gd 3+ , linear (Gd-DTPA, Magnevist) or cyclic (Dotarem) GBCAs. Transmembrane ion-currents (I M ) were recorded by the two-electrode-voltage-clamp technique and Gd 3+ -release by Gd-DTPA was confirmed by inductively coupled plasma-mass spectrometry. Gd 3+ exerts biphasic effects on ENaC's activity: ≤0.3mmol/l decreased I M which was preventable by DEPC (modifies histidines). Strikingly Gd 3+ ≥0.4mmol/l increased I M and this effect was prevented by cysteine-modifying MTSEA. Linear Gd-DTPA and Magnevist mimicked the effect of ≤0.3mmol/l Gd 3+ , whereas the chelator DTPA showed no effect. Gd 3+ and Gd-DTPA increased the IC 50 for amiloride, but did not affect ENaC's self-inhibition. Interestingly, cyclic Gd-DOTA (Dotarem) increased I M to a similar extent as its chelator DOTA, suggesting that the chelator rather than released Gd 3+ is responsible for this effect. These results confirm Gd 3+ -release from linear Gd-DTPA and indicate that the released Gd 3+ amount is sufficient to interfere with ENaC's activity to provide putative explanations for GBCA-related adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Long-term total sleep deprivation decreases the default spontaneous activity and connectivity pattern in healthy male subjects: a resting-state fMRI study

    Directory of Open Access Journals (Sweden)

    Dai XJ

    2015-03-01

    .33; P=0.021. The ICA method showed that, compared with RW subjects, SD subjects had decreased rsFC in the right inferior parietal lobule (IPL, BA40 and in the left precuneus (PrC/posterior cingulate cortex (PCC (BA30, 31. The two different areas were selected as regions of interest (ROIs for future rsFC analysis. Compared with the same in RW subjects, in SD subjects, the right IPL showed decreased rsFC with the left PrC (BA7 and increased rsFC with the left fusiform gyrus (BA37 and the left cluster of middle temporal gyrus and inferior temporal gyrus (BA37. However, the left PrC/PCC did not show any connectivity differences. Compared with RW subjects, SD subjects showed lower ALFF area in the left IPL (BA39, 40. The left IPL, as an ROI, showed decreased rsFC with the right cluster of IPL and superior temporal gyrus (BA39, 40. ROC curve analysis showed that the area under the curve (AUC value of the left IPL was 0.75, with a cutoff point of 0.834 (mean ALFF signal value. Further diagnostic analysis exhibited that the AUC alone discriminated SD status from RW status, with 75% sensitivity and 91.7% specificity. Conclusion: Long-term SD disturbed the spontaneous activity and connectivity pattern of DMN. Keywords: sleep deprivation, amplitude of low-frequency fluctuation, default-mode network, functional magnetic resonance imaging, functional connectivity, independent component analysis, receiver operating characteristic curve

  17. Overexpression of synapsin Ia in the rat calyx of Held accelerates short-term plasticity and decreases synaptic vesicle volume and active zone area

    Directory of Open Access Journals (Sweden)

    Mariya eVasileva

    2013-12-01

    Full Text Available Synapsins are synaptic vesicle (SV proteins organizing a component of the reserve pool of vesicles at most central nervous system synapses. Alternative splicing of the three mammalian genes results in multiple isoforms that may differentially contribute to the organization and maintenance of the synaptic vesicle-pools. To address this, we first characterized the expression pattern of synapsin isoforms in the rat calyx of Held. At postnatal day 16, synapsins Ia, Ib, IIb and IIIa were present, while IIa – known to sustain repetitive transmission in glutamatergic terminals – was not detectable. To test if the synapsin I isoforms could mediate IIa-like effect, and if this depends on the presence of the E-domain, we overexpressed either synapsin Ia or synapsin Ib in the rat calyx of Held via recombinant adeno-associated virus-mediated gene transfer. Although the size and overall structure of the perturbed calyces remained unchanged, short-term depression and recovery from depression were accelerated upon overexpression of synapsin I isoforms. Thus, at the calyx of Held, synapsin Ia may not substitute for the synapsin IIa-function reported for hippocampal synapses. Using electron microscopic three-dimensional reconstructions we found a redistribution of SV clusters proximal to the active zones (AZ alongside with a decrease of both AZ area and SV volume. The number of SVs at individual AZs was strongly reduced. Hence, our data indicate that the amount of synapsin Ia expressed in the calyx regulates the rate and extent of short-term synaptic plasticity by affecting vesicle recruitment to the AZ. Finally, our study reveals a novel contribution of synapsin Ia to define the surface area of AZs.

  18. Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro-inflammatory cytokines in human dendritic cells challenged with Salmonella typhi through TLR activation.

    Science.gov (United States)

    Bermudez-Brito, Miriam; Muñoz-Quezada, Sergio; Gomez-Llorente, Carolina; Matencio, Esther; Bernal, Maria J; Romero, Fernando; Gil, Angel

    2013-01-01

    Dendritic cells (DCs) constitute the first point of contact between gut commensals and our immune system. Despite growing evidence of the immunomodulatory effects of probiotics, the interactions between the cells of the intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of this work was to determine whether the probiotic Bifidobacterium breve CNCM I-4035 and its cell-free culture supernatant (CFS) have immunomodulatory effects in human intestinal-like dendritic cells (DCs) and how they respond to the pathogenic bacterium Salmonella enterica serovar Typhi, and also to elucidate the molecular mechanisms involved in these interactions. Human DCs were directly challenged with B. breve/CFS, S. typhi or a combination of these stimuli for 4 h. The expression pattern of genes involved in Toll-like receptor (TLR) signaling pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with S. typhi. In contrast, the B. breve CNCM I-4035 probiotic strain was a potent inducer of the pro-inflammatory cytokines and chemokines tested, i.e., TNF-α, IL-8 and RANTES, as well as anti-inflammatory cytokines including IL-10. CFS restored TGF-β levels in the presence of Salmonella. Live B.breve and its supernatant enhanced innate immune responses by the activation of TLR signaling pathway. These treatments upregulated TLR9 gene transcription. In addition, CFS was a more potent inducer of TLR9 expression than the probiotic bacteria in the presence of S. typhi. Expression levels of CASP8 and IRAK4 were also increased by CFS, and both treatments induced TOLLIP gene expression. Our results indicate that the probiotic strain B. breve CNCM I-4035 affects the intestinal immune response, whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This supernatant may protect immune system from highly infectious agents such as Salmonella typhi and can down-regulate pro

  19. Cell-free culture supernatant of Bifidobacterium breve CNCM I-4035 decreases pro-inflammatory cytokines in human dendritic cells challenged with Salmonella typhi through TLR activation.

    Directory of Open Access Journals (Sweden)

    Miriam Bermudez-Brito

    Full Text Available Dendritic cells (DCs constitute the first point of contact between gut commensals and our immune system. Despite growing evidence of the immunomodulatory effects of probiotics, the interactions between the cells of the intestinal immune system and bacteria remain largely unknown. Indeed,, the aim of this work was to determine whether the probiotic Bifidobacterium breve CNCM I-4035 and its cell-free culture supernatant (CFS have immunomodulatory effects in human intestinal-like dendritic cells (DCs and how they respond to the pathogenic bacterium Salmonella enterica serovar Typhi, and also to elucidate the molecular mechanisms involved in these interactions. Human DCs were directly challenged with B. breve/CFS, S. typhi or a combination of these stimuli for 4 h. The expression pattern of genes involved in Toll-like receptor (TLR signaling pathway and cytokine secretion was analyzed. CFS decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with S. typhi. In contrast, the B. breve CNCM I-4035 probiotic strain was a potent inducer of the pro-inflammatory cytokines and chemokines tested, i.e., TNF-α, IL-8 and RANTES, as well as anti-inflammatory cytokines including IL-10. CFS restored TGF-β levels in the presence of Salmonella. Live B.breve and its supernatant enhanced innate immune responses by the activation of TLR signaling pathway. These treatments upregulated TLR9 gene transcription. In addition, CFS was a more potent inducer of TLR9 expression than the probiotic bacteria in the presence of S. typhi. Expression levels of CASP8 and IRAK4 were also increased by CFS, and both treatments induced TOLLIP gene expression. Our results indicate that the probiotic strain B. breve CNCM I-4035 affects the intestinal immune response, whereas its supernatant exerts anti-inflammatory effects mediated by DCs. This supernatant may protect immune system from highly infectious agents such as Salmonella typhi and can down

  20. Olanzapine promotes fat accumulation in male rats by decreasing physical activity, repartitioning energy and increasing adipose tissue lipogenesis while impairing lipolysis.

    Science.gov (United States)

    Albaugh, V L; Judson, J G; She, P; Lang, C H; Maresca, K P; Joyal, J L; Lynch, C J

    2011-05-01

    Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; although these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose and worsened oral glucose and insulin tolerance, suggesting that these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring (14)C-2-deoxyglucose uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia, there was a tendency for increased (14)C-2-deoxyglucose uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately twofold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA, and as it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest that olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

  1. Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells

    NARCIS (Netherlands)

    Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

    2014-01-01

    Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell

  2. Elevated salivary IgA, decreased anxiety, and an altered oral microbiota are associated with active participation on an undergraduate athletic team.

    Science.gov (United States)

    Lamb, Ashley L; Hess, Debra E; Edenborn, Sherie; Ubinger, Elizabeth; Carrillo, Andres E; Appasamy, Pierette M

    2017-02-01

    Previous reports indicate that regular, but not excessive, exercise can moderate the response to anxiety and alter the immune response, therefore we hypothesized that college student athletes who were actively participating on an NCAA Division III athletics team ("in-season") would have lower levels of anxiety and higher salivary IgA levels than similar college athletes who were in their "off-season". NCAA Division III athletes participate in athletics at a level of intensity that is more moderate compared to other NCAA divisions. Alterations in the microbiome have been associated with alterations in psychosocial well-being and with exercise. Therefore, we also proposed that the oral microbiota would be different in "in-season" versus "off-season" athletes. In this pilot study, nineteen female students participating on a NCAA Division III athletic team (hockey="in-season"; soccer="off-season") were compared for level of fitness (modified Balke test of VO 2 max), salivary IgA levels by immunoassay, anxiety (using a GAD-7 survey), salivary cortisol levels by immunoassay, and numbers of culturable bacteria by growth of CFU/ml on blood agar, mitis salivarius agar and Staphylococcus 110 agar. The proportion of subjects reporting "severe anxiety" on an anxiety scale (GAD-7) were significantly greater in the "off-season" group compared to the "in-season" group (p=0.047, Chi-squared test). "In-season" athletes had significantly higher salivary IgA/total protein levels than "off-season" athletes (one-sided Student's t-test; p=0.03). Cortisol levels were not significantly different in the two groups. The total culturable bacteria counts were higher among "in-season" athletes (p=0.0455, Wilcoxon Rank Sum test), as measured by CFUs on blood agar plates, an estimate of total culturable bacteria, including pathogenic and non-pathogenic bacteria. In contrast, there was a decrease in the growth of bacteria from the oral cavity of the "in-season" athletes, when the growth of

  3. Fukushima- the aftermath. The japanese power consumption has significantly decreased to adapt to a fading nuclear activity. Enerdata- Energy Efficiency and Demand

    International Nuclear Information System (INIS)

    2012-01-01

    In this study, a series of analyses supported by graphs assess the power supply evolution in Japan since Fukushima, which has decreased by 11% of reactors in operation since December 2011. Measures implemented in summer 2011 to adapt demand to a lower supply and their significant impact on the power consumption are also analyzed. (authors)

  4. Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.

    NARCIS (Netherlands)

    Lemonnier, L.; Lazarenko, R.; Shuba, Y.; Thebault, S.C.; Roudbaraki, M.; Lepage, G.; Prevarskaya, N.; Skryma, R.

    2005-01-01

    Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant,

  5. A natural xanthone increases catalase activity but decreases NF-kappa B and lipid peroxidation in U-937 and HepG2 cell lines.

    Science.gov (United States)

    Sahoo, Binay K; Zaidi, Adeel H; Gupta, Pankaj; Mokhamatam, Raveendra B; Raviprakash, Nune; Mahali, Sidhartha K; Manna, Sunil K

    2015-10-05

    Mangiferin, a C-glycosyl xanthone, has shown anti-inflammatory, antioxidant, and anti-tumorigenic activities. In the present study, we investigated the molecular mechanism for the antioxidant property of mangiferin. Considering the role of nuclear transcription factor kappa B (NF-κB) in inflammation and tumorigenesis, we hypothesized that modulating its activity will be a viable therapeutic target in regulating the redox-sensitive ailments. Our results show that mangiferin blocks several inducers, such as tumor necrosis factor (TNF), lypopolysaccharide (LPS), phorbol-12-myristate-13-acetate (PMA) or hydrogen peroxide (H2O2) mediated NF-κB activation via inhibition of reactive oxygen species generation. In silico docking studies predicted strong binding energy of mangiferin to the active site of catalase (-9.13 kcal/mol), but not with other oxidases such as myeloperoxidase, glutathione peroxidase, or inducible nitric oxide synthase. Mangiferin increased activity of catalase by 44%, but had no effect on myeloperoxidase activity in vitro. Fluorescence spectroscopy further revealed the binding of mangiferin to catalase at the single site with binding constant and binding affinity of 3.1×10(-7) M(-1) and 1.046 respectively. Mangiferin also inhibits TNF-induced lipid peroxidation and thereby protects apoptosis. Hence, mangiferin with its ability to inhibit NF-κB and increase the catalase activity may prove to be a potent therapeutic. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Over-expression of CD8+ T-cell activation is associated with decreased CD4+ cells in patients seeking treatment of Alcohol Use Disorder.

    Science.gov (United States)

    Zuluaga, Paola; Sanvisens, Arantza; Martínez-Cáceres, Eva; Teniente, Aina; Tor, Jordi; Muga, Robert

    2017-11-01

    Harmful alcohol consumption may have an impact on the adaptive immune system through an imbalance in T cell subpopulations and changes in cell activation. We aimed to analyze profiles of CD4 and CD8T cell activation in patients with alcohol use disorder (AUD). We used a cross-sectional study with patients seeking treatment of the disorder. Blood samples for immunophenotyping were obtained at admission. Profiles of T cell activation were defined: (I) CD38 + /HLA-DR + , (II) CD38 + /HLA-DR - , (III) CD38 - /HLA-DR + , (IV) CD38 - /HLA-DR - and compared with healthy controls. We calculated a CD8 + T cell activation indicator (AI) that was defined as the quotient of non-activated cells (CD38 - /HLA-DR - ) and activated cells (CD38 + /HLA-DR + ). 60 patients were eligible (83%M); median age was 49 years [IQR: 44-54] and alcohol consumption was 145g/day [IQR: 90-205]. Mean±SD of CD38 + /HLA-DR - was 50.3±50.6 cells/μL in patients and 33.5±24.5 cells/μL in controls (p=0.03), for the CD38 - /HLA-DR + it was 61±62.2 cells/μL in patients and 21.2±17.3 cells/μL in controls (pcells/μL in patients and 10.8±10.3 cells/μL in controls (pcells, and the percentage of CD38 + /HLA-DR + CD8 + T cells (r=0.37, p=0.003; r=0.2, p=0.086, respectively). Patients with AUD have an increased expression of immune activation with respect to healthy individuals. This excess of activated CD8 + T cells correlates with the absolute CD4 + T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate decreased activation of reward-related brain centers in response to food cues in both the fed and fasting states: a preliminary fMRI study.

    Science.gov (United States)

    Farr, O M; Mantzoros, C S

    2017-03-01

    It remains unknown whether obese individuals with more components of the metabolic syndrome and/or prediabetes demonstrate altered activation of brain centers in response to food cues. We examined obese individuals with prediabetes (n=26) vs obese individuals without prediabetes (n=11) using fMRI. We also performed regression analyses on the basis of the number of MetS components per subject. Obese individuals with prediabetes have decreased activation of the reward-related putamen in the fasting state and decreased activation of the salience- and reward-related insula after eating. Obese individuals with more components of MetS demonstrate decreased activation of the putamen while fasting. All these activations remain significant when corrected for BMI, waist circumference (WC), HbA1c and gender. Decreased activation in the reward-related central nervous system areas among the obese is more pronounced in subjects with prediabetes and MetS. Prospective studies are needed to quantify their contributions to the development of prediabetes/MetS and to study whether they may predispose to the exacerbation of obesity and the development of comorbidities over time.

  8. Association between TPMT*3C and decreased thiopurine S-methyltransferase activity in patients with neuromyelitis optica spectrum disorders in China.

    Science.gov (United States)

    Gong, Xiaoqing; Mei, Shenghui; Li, Xindi; Li, Xingang; Zhou, Heng; Liu, Yonghong; Zhou, Anna; Yang, Li; Zhao, Zhigang; Zhang, Xinghu

    2018-06-01

    Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT*3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China. A liquid chromatography tandem mass/mass method was used to evaluate the thiopurine S-methyltransferase activity by using 6-mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by haematocrit and normalized to 8 × 10 8 erythrocytes. The selected polymorphisms of thiopurine S-methyltransferase were identified using MassARRAY system (Sequenom) and multiple SNaPshot technique. In 69 patients with neuromyelitis optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29-154.53 (127.51 ± 16.83) pmol/h/8 × 10 8 erythrocytes. TPMT*3C (rs1142345) was associated with lower thiopurine S-methyltransferase activity (BETA = -25.37, P = 0.011). Other selected variants were not associated with thiopurine S-methyltransferase activity. TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results. TPRs = thiopurines; NMOSD = neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase; LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6-methylmercaptopurine; IS = internal standard; SNP = single nucleotide polymorphism; MAF = minor allele frequency; HWE = Hardy-Weinberg equilibrium; BETA = regression coefficients; UTR-3 = untranslated region 3.

  9. 20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.

    Directory of Open Access Journals (Sweden)

    Zorica Janjetovic

    Full Text Available The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1 to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR, 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

  10. Parent-child intervention decreases stress and increases maternal brain activity and connectivity during own baby-cry: An exploratory study.

    Science.gov (United States)

    Swain, James E; Ho, S Shaun; Rosenblum, Katherine L; Morelen, Diana; Dayton, Carolyn J; Muzik, Maria

    2017-05-01

    Parental responses to their children are crucially influenced by stress. However, brain-based mechanistic understanding of the adverse effects of parenting stress and benefits of therapeutic interventions is lacking. We studied maternal brain responses to salient child signals as a function of Mom Power (MP), an attachment-based parenting intervention established to decrease maternal distress. Twenty-nine mothers underwent two functional magnetic resonance imaging brain scans during a baby-cry task designed to solicit maternal responses to child's or self's distress signals. Between scans, mothers were pseudorandomly assigned to either MP (n = 14) or control (n = 15) with groups balanced for depression. Compared to control, MP decreased parenting stress and increased child-focused responses in social brain areas highlighted by the precuneus and its functional connectivity with subgenual anterior cingulate cortex, which are key components of reflective self-awareness and decision-making neurocircuitry. Furthermore, over 13 weeks, reduction in parenting stress was related to increasing child- versus self-focused baby-cry responses in amygdala-temporal pole functional connectivity, which may mediate maternal ability to take her child's perspective. Although replication in larger samples is needed, the results of this first parental-brain intervention study demonstrate robust stress-related brain circuits for maternal care that can be modulated by psychotherapy.

  11. Ghrelin decreases firing activity of gonadotropin-releasing hormone (GnRH neurons in an estrous cycle and endocannabinoid signaling dependent manner.

    Directory of Open Access Journals (Sweden)

    Imre Farkas

    Full Text Available The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca(2+-imaging revealed a ghrelin-triggered increase of the Ca(2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10 µM suggesting direct action of ghrelin. Estradiol (1nM eliminated the ghrelin-evoked rise of Ca(2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40 nM-4 μM administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1 antagonist AM251 (1µM and the intracellularly applied DAG-lipase inhibitor THL (10 µM, indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner.

  12. Disease activity decrease is associated with improvement in work productivity over 1 year in early axial spondyloarthritis (SPondyloArthritis Caught Early cohort)

    NARCIS (Netherlands)

    van Lunteren, Miranda; Ez-Zaitouni, Zineb; Fongen, Camilla; Landewé, Robert; Ramonda, Roberta; van der Heijde, Désirée; van Gaalen, Floris A.

    2017-01-01

    To assess if a change in disease activity is associated with a change in work productivity loss (WPL) over 1 year in early axial SpA (axSpA) patients. Baseline and 1 year data of axSpA patients in the SPondyloArthritis Caught Early cohort were analysed. Linear regression models were built explaining

  13. A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl hydroxylase activity in an ehlers-danlos VIA patient

    NARCIS (Netherlands)

    Walker, L.C.; Overstreet, M.A.; Siddiqui, A.; Paepe, A. de; Ceylaner, G.; Malfait, F.; Symoens, S.; Atsawasuwan, P.; Yamauchi, M.; Ceylaner, S.; Bank, R.A.; Yeowell, H.N.

    2005-01-01

    The clinical diagnosis of a patient with the phenotype of Ehlers-Danlos syndrome type VI was confirmed biochemically by the severely diminished level of lysyl hydroxylase (LH) activity in the patient's skin fibroblasts. A novel homozygous mutation, a single base change of T1360 → G in exon 13 of the

  14. Local activation of uterine Toll-like receptor 2 and 2/6 decreases embryo implantation and affects uterine receptivity in mice.

    Science.gov (United States)

    Sanchez-Lopez, Javier Arturo; Caballero, Ignacio; Montazeri, Mehrnaz; Maslehat, Nasim; Elliott, Sarah; Fernandez-Gonzalez, Raul; Calle, Alexandra; Gutierrez-Adan, Alfonso; Fazeli, Alireza

    2014-04-01

    Embryo implantation is a complex interaction between maternal endometrium and embryonic structures. Failure to implant is highly recurrent and impossible to diagnose. Inflammation and infections in the female reproductive tract are common causes of infertility, embryo loss, and preterm labor. The current work describes how the activation of endometrial Toll-like receptor (TLR) 2 and 2/6 reduces embryo implantation chances. We developed a morphometric index to evaluate the effects of the TLR 2/6 activation along the uterine horn (UH). TLR 2/6 ligation reduced the endometrial myometrial and glandular indexes and increased the luminal index. Furthermore, TLR 2/6 activation increased the proinflammatory cytokines such as interleukin (IL)-1beta and monocyte chemotactic protein (MCP)-1 in UH lavages in the preimplantation day and IL-1 receptor antagonist in the implantation day. The engagement of TLR 2/6 with its ligand in the UH during embryo transfer severely affected the rate of embryonic implantation (45.00% ± 6.49% vs. 16.69% ± 5.01%, P embryo implantation process was verified using an in vitro model of human embryo implantation where trophoblast spheroids failed to adhere to a monolayer of TLR 2- and TLR 2/6-activated endometrial cells. The inhibition of TLR receptors 2 and 6 in the presence of their specific ligands restored the ability of the spheroids to bind to the endometrial cells. In conclusion, the activation of the innate immune system in the uterus at the time of implantation interfered with the endometrial receptivity and reduced the chances of implantation success.

  15. mTOR inhibition in macrophages of asymptomatic HIV+ persons reverses the decrease in TLR4-mediated TNFα release through prolongation of MAPK pathway activation1

    Science.gov (United States)

    Li, Xin; Han, Xinbing; Llano, Juliana; Bole, Medhavi; Zhou, Xiuqin; Swan, Katharine; Anandaiah, Asha; Nelson, Benjamin; Patel, Naimish R.; Reinach, Peter S.; Koziel, Henry; Tachado, Souvenir D.

    2011-01-01

    Toll-like receptor 4 (TLR4) mediated signaling is significantly impaired in macrophages from HIV+ persons predominantly due to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. Here we assessed in these macrophages if the blunted increase in TLR4-mediated TNFα release induced by lipid A are associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR4-mediated TNFα release, but instead suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in lipid A-induced TNFα and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88-IRAK interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (shRNA) and mTOR (RNAi) inhibition resulted in TLR4-mediated p70s6K activation and enhanced TNFα release, whereas IL-10 release was inhibited in both silenced and non-silenced HIV+ macrophages. Furthermore, mTOR inhibition augmented lipid A-induced TNFα release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAP kinases, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR4-mediated TNFα release in HIV+ macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MKP-1 stabilization, which shortens and blunts MAP kinase activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV+ persons. PMID:22025552

  16. Mutations in the Arabidopsis Lst8 and Raptor genes encoding partners of the TOR complex, or inhibition of TOR activity decrease abscisic acid (ABA) synthesis.

    Science.gov (United States)

    Kravchenko, Alena; Citerne, Sylvie; Jéhanno, Isabelle; Bersimbaev, Rakhmetkazhi I; Veit, Bruce; Meyer, Christian; Leprince, Anne-Sophie

    2015-11-27

    The Target of Rapamycin (TOR) kinase regulates essential processes in plant growth and development by modulation of metabolism and translation in response to environmental signals. In this study, we show that abscisic acid (ABA) metabolism is also regulated by the TOR kinase. Indeed ABA hormone level strongly decreases in Lst8-1 and Raptor3g mutant lines as well as in wild-type (WT) Arabidopsis plants treated with AZD-8055, a TOR inhibitor. However the growth and germination of these lines are more sensitive to exogenous ABA. The diminished ABA hormone accumulation is correlated with lower transcript levels of ZEP, NCED3 and AAO3 biosynthetic enzymes, and higher transcript amount of the CYP707A2 gene encoding a key-enzyme in abscisic acid catabolism. These results suggest that the TOR signaling pathway is implicated in the regulation of ABA accumulation in Arabidopsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Decreasing Relative Risk Premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    relative risk premium in the small implies decreasing relative risk premium in the large, and decreasing relative risk premium everywhere implies risk aversion. We finally show that preferences with decreasing relative risk premium may be equivalently expressed in terms of certain preferences on risky......We consider the risk premium demanded by a decision maker with wealth x in order to be indifferent between obtaining a new level of wealth y1 with certainty, or to participate in a lottery which either results in unchanged present wealth or a level of wealth y2 > y1. We define the relative risk...... premium as the quotient between the risk premium and the increase in wealth y1–x which the decision maker puts on the line by choosing the lottery in place of receiving y1 with certainty. We study preferences such that the relative risk premium is a decreasing function of present wealth, and we determine...

  18. Coherent anti-Stokes Raman scattering (CARS) spectroscopy in Caenorhabditis elegans and Globodera pallida: evidence for an ivermectin-activated decrease in lipid stores.

    Science.gov (United States)

    Smus, Justyna P; Ludlow, Elizabeth; Dallière, Nicolas; Luedtke, Sarah; Monfort, Tual; Lilley, Catherine; Urwin, Peter; Walker, Robert J; O'Connor, Vincent; Holden-Dye, Lindy; Mahajan, Sumeet

    2017-12-01

    Macrocyclic lactones are arguably the most successful chemical class with efficacy against parasitic nematodes. Here we investigated the effect of the macrocyclic lactone ivermectin on lipid homeostasis in the plant parasitic nematode Globodera pallida and provide new insight into its mode of action. A non-invasive, non-destructive, label-free and chemically selective technique called Coherent anti-Stokes Raman scattering (CARS) spectroscopy was used to study lipid stores in G. pallida. We optimised the protocol using the free-living nematode Caenorhabditis elegans and then used CARS to quantify lipid stores in the pre-parasitic, non-feeding J2 stage of G. pallida. This revealed a concentration of lipid stores in the posterior region of J2 s within 24 h of hatching which decreased to undetectable levels over the course of 28 days. We tested the effect of ivermectin on J2 viability and lipid stores. Within 24 h, ivermectin paralysed J2 s. Counterintuitively, over the same time-course ivermectin increased the rate of depletion of J2 lipid, suggesting that in ivermectin-treated J2 s there is a disconnection between the energy requirements for motility and metabolic rate. This decrease in lipid stores would be predicted to negatively impact on J2 infective potential. These data suggest that the benefit of macrocyclic lactones as seed treatments may be underpinned by a multilevel effect involving both neuromuscular inhibition and acceleration of lipid metabolism. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  19. Decreasing Serial Cost Sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter

    The increasing serial cost sharing rule of Moulin and Shenker [Econometrica 60 (1992) 1009] and the decreasing serial rule of de Frutos [Journal of Economic Theory 79 (1998) 245] have attracted attention due to their intuitive appeal and striking incentive properties. An axiomatic characterization...... of the increasing serial rule was provided by Moulin and Shenker [Journal of Economic Theory 64 (1994) 178]. This paper gives an axiomatic characterization of the decreasing serial rule...

  20. Decreasing serial cost sharing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2009-01-01

    The increasing serial cost sharing rule of Moulin and Shenker (Econometrica 60:1009-1037, 1992) and the decreasing serial rule of de Frutos (J Econ Theory 79:245-275, 1998) are known by their intuitive appeal and striking incentive properties. An axiomatic characterization of the increasing serial...... rule was provided by Moulin and Shenker (J Econ Theory 64:178-201, 1994). This paper gives an axiomatic characterization of the decreasing serial rule....

  1. The characteristics of the Third Sector in Ukraine. Increases and decreases in the activity of particular organizations and the policy of the ruling elite

    Directory of Open Access Journals (Sweden)

    Kamila Pytlik

    2015-09-01

    Full Text Available The main subject of this article is the activity of non-governmental organizations in Ukraine and their role in the life democratization. The article includes methods of financing non-governmental organizations and the influence of domestic and foreign subsidies for their work. Moreover, it raises a question about ethical behaviour of people, that finance these organizations and reveals the political aspects of the decisions which were made. It depicts the development dynamics of NGOs during several years. Furthermore, it emphasizes the increase of activity of all members of the NGOs during the Orange Revolution and the stagnation caused by the political crisis in 2007. This work indicates what is the stimulus for the development of Ukrainian NGOs.

  2. Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway.

    Science.gov (United States)

    Gao, Yali; Lu, Xiaohe

    2016-02-01

    The aberrant expression of MEG3 has been found in some types of cancers; however, little is known concerning the function of MEG3 in retinoblastoma. To elucidate the roles of MEG3 in retinoblastoma, MEG3 expression was quantified in 63 retinoblastoma samples and corresponding nontumor tissues in this work. Moreover, retinoblastoma cell lines were transfected with pcDNA3.1-MEG3 or si-MEG3, after which proliferation, apoptosis, and expression of β-catenin were assayed. TOP-Flash reporter assay was also used to investigate the activity of the Wnt/β-catenin pathway. The results showed that MEG3 was downregulated in retinoblastoma tissues, and the level of MEG3 was negatively associated with IIRC stages and nodal or distant metastasis. More importantly, Kaplan-Meier survival analysis demonstrated that patients with low MEG3 expression had poorer survival and multivariate Cox regression analysis revealed that MEG3 was an independent prognostic factor in retinoblastoma patients. We also observed that MEG3 expression can be modulated by DNA methylation by using 5-aza-CdR treatment. In addition, overexpression of MEG3 suppressed proliferation, promoted apoptosis, and influences the activity of the Wnt/β-catenin pathway in retinoblastoma cell lines. Furthermore, we found that Wnt/β-catenin pathway activator rescued the anticancer effect of MEG3 in retinoblastoma. In conclusion, our study for the first time demonstrated that MEG3 was a tumor suppressor by negatively regulating the activity of the Wnt/β-catenin pathway in the progression of retinoblastoma and might serve as a prognostic biomarker and molecular therapeutic target.

  3. Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Agata Stanek

    2018-01-01

    Full Text Available Objective. The aim of the study was to estimate the impact of whole-body cryotherapy (WBC on cardiovascular risk factors in patients with ankylosing spondylitis (AS. Material and Methods. We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group. To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT group. Results. The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion. WBC appears to be a useful method of atherosclerosis prevention in AS patients.

  4. [Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

    Science.gov (United States)

    Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

    2012-03-01

    Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

  5. Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

    Science.gov (United States)

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

    2015-02-01

    Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

  6. Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.

    Science.gov (United States)

    Egbert, Jeremy R; Yee, Siu-Pok; Jaffe, Laurinda A

    2018-03-01

    Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Fourth ventricle injection of ghrelin decreases angiotensin II-induced fluid intake and neuronal activation in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Plyler, Kimberly S; Daniels, Derek

    2017-09-01

    Ghrelin acts in the CNS to decrease fluid intake under a variety of dipsogenic and natriorexigenic conditions. Previous studies on this topic, however, focused on the forebrain as a site of action for this effect of ghrelin. Because the hindbrain contains neural substrates that are capable of mediating the well-established orexigenic effects of ghrelin, the current study tested the hypothesis that ghrelin applied to the hindbrain also would affect fluid intake. To this end, water and saline intakes were stimulated by central injection of angiotensin II (AngII) in rats that also received injections of ghrelin (0.5μg/μl) into either the lateral or fourth ventricle. Ghrelin injected into either ventricle reduced both water and 1.8% NaCl intake that was stimulated by AngII. The nature of the intake effect revealed some differences between the injection sites. For example, forebrain application of ghrelin reduced saline intake by a reduction in both the number of licking bursts and the size of each licking burst, but hindbrain application of ghrelin had a more selective effect on burst number. In an attempt to elucidate a brain structure in which hindbrain-administered ghrelin and forebrain-administered AngII interact to cause the ingestive response, we used Fos-immunohistochemistry in rats given the treatments used in the behavioral experiments. Although several brain areas were found to respond to either ghrelin or AngII, of the sites examined, only the paraventricular nucleus of the hypothalamus (PVN) emerged as a potential site of interaction. Specifically, AngII treatment caused expression of Fos in the PVN that was attenuated by concomitant treatment with ghrelin. These experiments provide the novel finding that the hindbrain contains elements that can respond to ghrelin and cause decreases in AngII-induced fluid intake, and that direct actions by ghrelin on forebrain structures is not necessary. Moreover, these studies suggest that the PVN is an important site

  8. Phosphorylation of protein kinase C sites Ser42/44 decreases Ca2+-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes

    NARCIS (Netherlands)

    Wijnker, P.J.M.; Sequeira Oliveira, V.; Witjas-Paalberends, E.R.; Foster, D.B.; dos Remedios, C.G.; Murphy, A.M.; Stienen, G.J.M.; van der Velden, J.

    2014-01-01

    Protein kinase C (PKC)-mediated phosphorylation of troponin I (cTnI) at Ser42/44 is increased in heart failure. While studies in rodents demonstrated that PKC-mediated Ser42/44 phosphorylation decreases maximal force and ATPase activity, PKC incubation of human cardiomyocytes did not affect maximal

  9. BLOCKADE OF ROSTRAL VENTROLATERAL MEDULLA (RVLM BOMBESIN RECEPTOR TYPE 1 DECREASES BLOOD PRESSURE AND SYMPATHETIC ACTIVITY IN ANESTHETIZED SPONTANEOUSLY HYPERTENSIVE RATS

    Directory of Open Access Journals (Sweden)

    Izabella Silva De Jesus Pinto

    2016-06-01

    Full Text Available IIntrathecal injection of bombesin (BBS promoted hypertensive and sympathoexcitatory effects in normotensive (NT rats. However, the involvement of rostral ventrolateral medulla (RVLM in these responses is still unclear. In the present study, we investigated: (1 the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR; (2 the contribution of RVLM bombesin type 1 receptors (BB1 to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg−1, i.v. were instrumented to record mean arterial pressure (MAP, diaphragm (DIA motor and renal sympathetic nerve activity (RSNA. In NT rats and SHR, BBS (0.3 mM nanoinjected into RVLM increased MAP (33.9 ± 6.6 mmHg and 37.1 ± 4.5 mmHg, respectively; p < 0.05 and RSNA (97.8 ± 12.9 % and 84.5 ± 18.1 %, respectively; p < 0.05. In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7 %; p < 0.05. BB1 receptors antagonist (BIM-23127; 3 mM reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05 and RSNA (-17.7 ± 3.8 %; p < 0.05 in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6 %, respectively. These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

  10. GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice

    OpenAIRE

    Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

    2014-01-01

    The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17beta estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improv...

  11. Activity assay of mangosteen (Garcinia mangostana L.) pericarp extract for decreasing fasting blood cholesterol level and lipid peroxidation in type-2 diabetic mice

    Science.gov (United States)

    Husen, Saikhu Akhmad; Winarni, Dwi; Khaleyla, Firas; Kalqutny, Septian Hary; Ansori, Arif Nur Muhammad

    2017-09-01

    This study aimed to explore the activity of pericarp extract of mangosteen (Garcinia mangostana L.). Mangosteen pericarp contains various active compounds which are beneficial for human health. In-vivo antioxidant assay of pericarp extract was carried out using 3-4 month male mice of strain BALB/c weighed 30-40 g. The mice were divided into two groups: normal control (KN) group and STZ-induced diabetic group. STZ induction was performed using multiple low-dose method 30 mg/kg body weight treated daily for five consecutive days. Diabetic group was separated into two subgroups: diabetic control (KD), metformin control (KM), and crude extract treatment subgroups. The fasting blood glucose and the cholesterol level were measured before and after lard treatment, we also did it on the first, seventh, and fourteenth day of mangosteen pericarp crude extract treatment. The mice were treated with mangosteen pericarp crude extract for 14 days. The MDA level of the fasting blood serum was measured. The body weight and fasting blood cholesterol level before and after lard treatment were analyzed by t-test, whereas, the fasting blood cholesterol and the MDA level were analyzed using one-way variant analysis continued with Duncan test. The correlation between the increasing body weight and the fasting blood cholesterol level was determined by Pearson correlation test. The results of the study showed that the administration of mangosteen pericarp crude extract was able to reduce the fasting blood cholesterol and the malondialdehide level significantly.

  12. GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice.

    Science.gov (United States)

    Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

    2014-01-01

    The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17β estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition. In this study, we investigated the effect of a similar chronic administration of G-1 on behaviors that denote anxiety in adult ovariectomized female mice, using the elevated plus maze (EPM) and the open field test as well as the activation of the ERK pathway in the hippocampus. Although estradiol benzoate had no effect on behaviors in the EPM or the open field, G-1 had an anxiolytic effect solely in the open field that was independent of ERK signaling in either the ventral or dorsal hippocampus. Such an anxiolytic effect may underlie the ability of G-1 to increase spatial memory, by acting on the hippocampus.

  13. Saccharomyces boulardii expresses neuraminidase activity selective for α2,3-linked sialic acid that decreases Helicobacter pylori adhesion to host cells.

    Science.gov (United States)

    Sakarya, Serhan; Gunay, Necati

    2014-10-01

    Helicobacter pylori is a major causative agent of gastritis and peptic ulcer disease and is an established risk factor for gastric malignancy. Antibiotic combination therapy can eradicate H. pylori. As these same regimens can evoke adverse effects and resistance, new alternative therapies or adjunctive treatments are needed. A probiotic approach may provide a novel strategy for H. pylori treatment. In the current study, two probiotic bacteria, Lactobacillus acidophilus and Lactobacillus reuteri, and a probiotic yeast, Saccharomyces boulardii, were evaluated for their ability to influence H. pylori viability, adherence to gastric and duodenal cells, as well as the effect of S. boulardii on cell surface expression of sialic acid. Our results indicate that S. boulardii contains neuraminidase activity selective for α(2-3)-linked sialic acid. This neuraminidase activity removes surface α(2-3)-linked sialic acid, the ligand for the sialic acid-binding H. pylori adhesin, which in turn, inhibits H. pylori adherence to duodenal epithelial cells. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  14. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  15. Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

    Science.gov (United States)

    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-07-05

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

    Science.gov (United States)

    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-01-01

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

  17. Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

    Directory of Open Access Journals (Sweden)

    Ayyalasomayajula Vajreswari

    2011-06-01

    Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

  18. Fatness predicts decreased physical activity and increased sedentary time, but not vice versa: support from a longitudinal study in 8- to 11-year-old children

    DEFF Research Database (Denmark)

    Hjorth, M. F.; Chaput, J.-P.; Ritz, C.

    2014-01-01

    and FMI. Methods: Cross-sectional and longitudinal analyses were done using data from the OPUS school meal study on 785 children (52% boys, 13.4% overweight, ages 8–11 years). Total PA, moderate-to-vigorous PA (MVPA), sedentary time and sleep duration (7 days and 8 nights) were assessed......Objective: To examine independent and combined cross-sectional associations between movement behaviors (physical activity (PA), sedentary time, sleep duration, screen time and sleep disturbance) and fat mass index (FMI), as well as to examine longitudinal associations between movement behaviors...... by an accelerometer and FMI was determined by dual-energy X-ray absorptiometry (DXA) on three occasions over 200 days. Demographic characteristics, screen time and sleep disturbance (Children’s Sleep Habits Questionnaire) were also obtained. Results: Total PA, MVPA and sleep duration were negatively associated...

  19. A Novel Apolipoprotein C-II Mimetic Peptide That Activates Lipoprotein Lipase and Decreases Serum Triglycerides in Apolipoprotein E–Knockout Mice

    Science.gov (United States)

    Sakurai, Toshihiro; Sakurai-Ikuta, Akiko; Sviridov, Denis; Freeman, Lita; Ahsan, Lusana; Remaley, Alan T.

    2015-01-01

    Apolipoprotein A-I (apoA-I) mimetic peptides are currently being developed as possible new agents for the treatment of cardiovascular disease based on their ability to promote cholesterol efflux and their other beneficial antiatherogenic properties. Many of these peptides, however, have been reported to cause transient hypertriglyceridemia due to inhibition of lipolysis by lipoprotein lipase (LPL). We describe a novel bihelical amphipathic peptide (C-II-a) that contains an amphipathic helix (18A) for binding to lipoproteins and stimulating cholesterol efflux as well as a motif based on the last helix of apolipoprotein C-II (apoC-II) that activates lipolysis by LPL. The C-II-a peptide promoted cholesterol efflux from ATP-binding cassette transporter ABCA1-transfected BHK cells similar to apoA-I mimetic peptides. Furthermore, it was shown in vitro to be comparable to the full-length apoC-II protein in activating lipolysis by LPL. When added to serum from a patient with apoC-II deficiency, it restored normal levels of LPL-induced lipolysis and also enhanced lipolysis in serum from patients with type IV and V hypertriglyceridemia. Intravenous injection of C-II-a (30 mg/kg) in apolipoprotein E–knockout mice resulted in a significant reduction of plasma cholesterol and triglycerides of 38 ± 6% and 85 ± 7%, respectively, at 4 hours. When coinjected with the 5A peptide (60 mg/kg), the C-II-a (30 mg/kg) peptide was found to completely block the hypertriglyceridemic effect of the 5A peptide in C57Bl/6 mice. In summary, C-II-a is a novel peptide based on apoC-II, which promotes cholesterol efflux and lipolysis and may therefore be useful for the treatment of apoC-II deficiency and other forms of hypertriglyceridemia. PMID:25395590

  20. Decreasing relative risk premium

    DEFF Research Database (Denmark)

    Hansen, Frank

    2007-01-01

    such that the corresponding relative risk premium is a decreasing function of present wealth, and we determine the set of associated utility functions. We find a new characterization of risk vulnerability and determine a large set of utility functions, closed under summation and composition, which are both risk vulnerable...

  1. Decreasing asthma morbidity

    African Journals Online (AJOL)

    1994-12-12

    Dec 12, 1994 ... Apart from the optimal use of drugs, various supplementary methods have been tested to decrease asthma morbidity, usually in patients from reiatively affluent socio-economic backgrounds. A study of additional measures taken in a group of moderate to severe adult asthmatics from very poor socio- ...

  2. P2X7 receptor blockade protects against cisplatin-induced nephrotoxicity in mice by decreasing the activities of inflammasome components, oxidative stress and caspase-3

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuanyuan; Yuan, Fahuan; Cao, Xuejiao [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Zhai, Zhifang [Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Gang Huang [Department of Medical Genetics, Third Military Medical University, Chongqing 430038 (China); Du, Xiang; Wang, Yiqin; Zhang, Jingbo; Huang, Yunjian; Zhao, Jinghong [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China); Hou, Weiping, E-mail: hwp0518@aliyun.com [Department of Nephrology, Xinqiao Hospital, PLA, Third Military Medical University, Chongqing 400037 (China)

    2014-11-15

    Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. The purinergic 2X7 receptor (P2X7R) plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the expression of P2X7R in cisplatin-induced nephrotoxicity in C57BL/6 mice, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after P2X7R blockade in vivo using an antagonist A-438079. Moreover, we measured the changes of nod-like receptor family, pyrin domain containing proteins (NLRP3) inflammasome components, oxidative stress, and proapoptotic genes in renal tissues in cisplatin-induced nephrotoxicity after treatment with A-438079. We found that the expression of P2X7R was significantly upregulated in the renal tubular epithelial cells in cisplatin-induced nephrotoxicity compared with that of the normal control group. Furthermore, pretreatment with A-438079 markedly attenuated the cisplatin-induced renal injury while lightening the histological damage, inflammatory response and apoptosis in renal tissue, and improved the renal function. These effects were associated with the significantly reduced levels of NLRP3 inflammasome components, oxidative stress, p53 and caspase-3 in renal tissues in cisplatin-induced nephrotoxicity. In conclusions, our studies suggest that the upregulated activity of P2X7R might play important roles in the development of cisplatin-induced nephrotoxicity, and P2X7R blockade might become an effective therapeutic strategy for this disease. - Highlights: • The P2X7R expression was markedly upregulated in cisplatin-induced nephrotoxicity. • P2X7R blockade significantly attenuated the cisplatin-induced renal injury. • P2X7R blockade reduced activities of NLRP3 inflammasome components in renal tissue. • P2X7R blockade

  3. Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells.

    Science.gov (United States)

    Kappus, Mojdeh S; Murphy, Andrew J; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L; Tall, Alan R; Westerterp, Marit

    2014-02-01

    Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell deficiency of ATP-binding cassette transporters A1 and G1 (ABCA1/G1), principal targets of LXR that promote macrophage cholesterol efflux and initiate reverse cholesterol transport, would abolish the beneficial effects of LXR activation on atherosclerosis. LXR activator T0901317 substantially reduced inflammatory gene expression in macrophages lacking ABCA1/G1. Ldlr(-/-) mice were transplanted with Abca1(-/-)Abcg1(-/-) or wild-type bone marrow (BM) and fed a Western-type diet for 6 weeks with or without T0901317 supplementation. Abca1/g1 BM deficiency increased atherosclerotic lesion complexity and inflammatory cell infiltration into the adventitia and myocardium. T0901317 markedly decreased lesion area, complexity, and inflammatory cell infiltration in the Abca1(-/-)Abcg1(-/-) BM-transplanted mice. To investigate whether this was because of macrophage Abca1/g1 deficiency, Ldlr(-/-) mice were transplanted with LysmCreAbca1(fl/fl)Abcg1(fl/fl) or Abca1(fl/fl)Abcg1(fl/fl) BM and fed Western-type diet with or without the more specific LXR agonist GW3965 for 12 weeks. GW3965 decreased lesion size in both groups, and the decrease was more prominent in the LysmCreAbca1(fl/fl)Abcg1(fl/fl) group. The results suggest that anti-inflammatory effects of LXR activators are of key importance to their antiatherosclerotic effects in vivo independent of cholesterol efflux pathways mediated by macrophage ABCA1/G1. This has implications for the development of LXR activators that lack adverse effects on lipogenic genes while maintaining the ability to transrepress inflammatory genes.

  4. Hair Dyes Resorcinol and Lawsone Reduce Production of Melanin in Melanoma Cells by Tyrosinase Activity Inhibition and Decreasing Tyrosinase and Microphthalmia-Associated Transcription Factor (MITF Expression

    Directory of Open Access Journals (Sweden)

    Shu-Mei Lee

    2015-01-01

    Full Text Available Hair coloring products are one of the most important cosmetics for modern people; there are three major types of hair dyes, including the temporary, semi-permanent and permanent hair dyes. The selected hair dyes (such as ammonium persulfate, sodium persulfate, resorcinol and lawsone are the important components for hair coloring products. Therefore, we analyzed the effects of these compounds on melanogenesis in B16-F10 melanoma cells. The results proved that hair dyes resorcinol and lawsone can reduce the production of melanin. The results also confirmed that resorcinol and lawsone inhibit mushroom and cellular tyrosinase activities in vitro. Resorcinol and lawsone can also downregulate the protein levels of tyrosinase and microphthalmia-associated transcription factor (MITF in B16-F10 cells. Thus, we suggest that frequent use of hair dyes may have the risk of reducing natural melanin production in hair follicles. Moreover, resorcinol and lawsone may also be used as hypopigmenting agents to food, agricultural and cosmetic industry in the future.

  5. Paternal care decreases foraging activity and body condition, but does not impose survival costs to caring males in a Neotropical arachnid.

    Science.gov (United States)

    Requena, Gustavo S; Buzatto, Bruno A; Martins, Eduardo G; Machado, Glauco

    2012-01-01

    Exclusive paternal care is the rarest form of parental investment in nature and theory predicts that the maintenance of this behavior depends on the balance between costs and benefits to males. Our goal was to assess costs of paternal care in the harvestman Iporangaia pustulosa, for which the benefits of this behavior in terms of egg survival have already been demonstrated. We evaluated energetic costs and mortality risks associated to paternal egg-guarding in the field. We quantified foraging activity of males and estimated how their body condition is influenced by the duration of the caring period. Additionally, we conducted a one-year capture-mark-recapture study and estimated apparent survival probabilities of caring and non-caring males to assess potential survival costs of paternal care. Our results indicate that caring males forage less frequently than non-caring individuals (males and females) and that their body condition deteriorates over the course of the caring period. Thus, males willing to guard eggs may provide to females a fitness-enhancing gift of cost-free care of their offspring. Caring males, however, did not show lower survival probabilities when compared to both non-caring males and females. Reduction in mortality risks as a result of remaining stationary, combined with the benefits of improving egg survival, may have played an important and previously unsuspected role favoring the evolution of paternal care. Moreover, males exhibiting paternal care could also provide an honest signal of their quality as offspring defenders, and thus female preference for caring males could be responsible for maintaining the trait.

  6. Paternal care decreases foraging activity and body condition, but does not impose survival costs to caring males in a Neotropical arachnid.

    Directory of Open Access Journals (Sweden)

    Gustavo S Requena

    Full Text Available Exclusive paternal care is the rarest form of parental investment in nature and theory predicts that the maintenance of this behavior depends on the balance between costs and benefits to males. Our goal was to assess costs of paternal care in the harvestman Iporangaia pustulosa, for which the benefits of this behavior in terms of egg survival have already been demonstrated. We evaluated energetic costs and mortality risks associated to paternal egg-guarding in the field. We quantified foraging activity of males and estimated how their body condition is influenced by the duration of the caring period. Additionally, we conducted a one-year capture-mark-recapture study and estimated apparent survival probabilities of caring and non-caring males to assess potential survival costs of paternal care. Our results indicate that caring males forage less frequently than non-caring individuals (males and females and that their body condition deteriorates over the course of the caring period. Thus, males willing to guard eggs may provide to females a fitness-enhancing gift of cost-free care of their offspring. Caring males, however, did not show lower survival probabilities when compared to both non-caring males and females. Reduction in mortality risks as a result of remaining stationary, combined with the benefits of improving egg survival, may have played an important and previously unsuspected role favoring the evolution of paternal care. Moreover, males exhibiting paternal care could also provide an honest signal of their quality as offspring defenders, and thus female preference for caring males could be responsible for maintaining the trait.

  7. A new mother-child play activity program to decrease parenting stress and improve child cognitive abilities: a cluster randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Tachibana

    Full Text Available BACKGROUND: We propose a new play activity intervention program for mothers and children. Our interdisciplinary program integrates four fields of child-related sciences: neuroscience, preschool pedagogy, developmental psychology, and child and maternal psychiatry. To determine the effect of this intervention on child and mother psychosocial problems related to parenting stress and on the children's cognitive abilities, we performed a cluster randomized controlled trial. METHODOLOGY/PRINCIPAL FINDINGS: Participants were 238 pairs of mothers and typically developing preschool children (ages 4-6 years old from Wakakusa kindergarten in Japan. The pairs were asked to play at home for about 10 min a day, 5 days a week for 3 months. Participants were randomly assigned to the intervention or control group by class unit. The Parenting Stress Index (PSI (for mothers, the Goodenough Draw-a-Man intelligence test (DAM, and the new S-S intelligence test (NS-SIT (for children were administered prior to and 3 months after the intervention period. Pre-post changes in test scores were compared between the groups using a linear mixed-effects model analysis. The primary outcomes were the Total score on the child domain of the PSI (for child psychosocial problems related to parenting stress, Total score on the parent domain of the PSI (for maternal psychosocial problems related to parenting stress, and the score on the DAM (for child cognitive abilities. The results of the PSI suggested that the program may reduce parenting stress. The results of the cognitive tests suggested that the program may improve the children's fluid intelligence, working memory, and processing speed. CONCLUSIONS/SIGNIFICANCE: Our intervention program may ameliorate the children's psychosocial problems related to parenting stress and increase their cognitive abilities. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000002265.

  8. A new mother-child play activity program to decrease parenting stress and improve child cognitive abilities: a cluster randomized controlled trial.

    Science.gov (United States)

    Tachibana, Yoshiyuki; Fukushima, Ai; Saito, Hitomi; Yoneyama, Satoshi; Ushida, Kazuo; Yoneyama, Susumu; Kawashima, Ryuta

    2012-01-01

    We propose a new play activity intervention program for mothers and children. Our interdisciplinary program integrates four fields of child-related sciences: neuroscience, preschool pedagogy, developmental psychology, and child and maternal psychiatry. To determine the effect of this intervention on child and mother psychosocial problems related to parenting stress and on the children's cognitive abilities, we performed a cluster randomized controlled trial. Participants were 238 pairs of mothers and typically developing preschool children (ages 4-6 years old) from Wakakusa kindergarten in Japan. The pairs were asked to play at home for about 10 min a day, 5 days a week for 3 months. Participants were randomly assigned to the intervention or control group by class unit. The Parenting Stress Index (PSI) (for mothers), the Goodenough Draw-a-Man intelligence test (DAM), and the new S-S intelligence test (NS-SIT) (for children) were administered prior to and 3 months after the intervention period. Pre-post changes in test scores were compared between the groups using a linear mixed-effects model analysis. The primary outcomes were the Total score on the child domain of the PSI (for child psychosocial problems related to parenting stress), Total score on the parent domain of the PSI (for maternal psychosocial problems related to parenting stress), and the score on the DAM (for child cognitive abilities). The results of the PSI suggested that the program may reduce parenting stress. The results of the cognitive tests suggested that the program may improve the children's fluid intelligence, working memory, and processing speed. Our intervention program may ameliorate the children's psychosocial problems related to parenting stress and increase their cognitive abilities. UMIN Clinical Trials Registry UMIN000002265.

  9. Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells.

    Science.gov (United States)

    Maxwell, Thressi; Lee, Kyu Shik; Kim, Soyoung; Nam, Kyung-Soo

    2018-04-01

    Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer. First, we found that arctigenin inhibited the viability of the MCF-7 cells, and colony formation assay confirmed that this effect was cytotoxic rather than cytostatic. The cytotoxic effects were not mediated by cell cycle arrest, apoptosis, or necroptosis, despite DNA damage, as indicated by poly(ADP-ribose) polymerase (PARP) cleavage and phosphorylated H2A.X. An increase in lipidated LC3, a marker of autophagosome formation, was observed, indicating that autophagy was induced by arctigenin, which was found to be triggered by the inhibition of the mechanistic target of rapamycin (mTOR) pathway. We then examined the effects of arctigenin on ERα expression and determined whether it affects the sensitivity of the cells to tamoxifen, as tamoxifen is commonly used against hormone-responsive cancers and is known to act via the ERα. We found that treatment with arctigenin effectively downregulated ERα expression, which was found to be a consequence of the inhibition of the mTOR pathway. However, treatment with arctigenin in combination with tamoxifen did not affect the sensitivity of the cells to tamoxifen, but instead, exerted a synergistic effect. On the whole, our data indicate that the phytoestrogen, arctigenin, mainly targeted the mTOR pathway in ERα-positive MCF-7 human breast cancer cells, leading to autophagy-induced cell death and the downregulation of ERα expression. Furthermore, the synergistic effects

  10. Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort.

    Science.gov (United States)

    Durán-Barragán, S; McGwin, G; Vilá, L M; Reveille, J D; Alarcón, G S

    2008-07-01

    To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

  11. [Why is bread consumption decreasing?].

    Science.gov (United States)

    Rolland, M F; Chabert, C; Serville, Y

    1977-01-01

    In France bread plays a very special and ambivalent role among our foodstuffs because of the considerable drop in its consumption, its alleged harmful effects on our health and the respect in which it is traditionally held. More than half the 1 089 adults interviewed in this study say they have decreased their consumption of bread in the last 10 years. The reasons given vary according to age, body weight and urbanization level. The main reasons given for this restriction are the desire to prevent or reduce obesity, the decrease in physical activity, the general reduction in food consumption and the possibility of diversifying foods even further. Moreover, the decreasing appeal of bread in relation to other foods, as well as a modification in the structure of meals, in which bread becomes less useful to accompany other food, accentuate this loss of attraction. However, the respect for bread as part of the staple diet remains very acute as 95 p. 100 of those interviewed express a reluctance to throw bread away, more for cultural than economic reasons. Mechanization and urbanization having brought about a decrease in energy needs, the most common alimentary adaptation is general caloric restriction by which glucids, and especially bread, are curtailed.

  12. Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T-cells and decrease of ''naive'' (CD4-CD45R) T lymphocytes

    International Nuclear Information System (INIS)

    De Ruysscher, D.; Aerts, R.; Vantongelen, K.; Schueren, E. van der; Waer, M.; Vandeputte, M.

    1992-01-01

    Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or ''memory'' T cells recovered completely, while the CD4-45R or ''naive'' T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells (''activated'' T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. The authors propose that recovery of the CD4 cells is limited to the CD4-w29 (''memory'') population because of thymic dysfunction in older humans. (Author)

  13. The Green Tea Component (--Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Directory of Open Access Journals (Sweden)

    Jee-Youn Kim

    Full Text Available The green tea component (--epigallocatechin-3-gallate (EGCG has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose polymerase (PARP, activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As treatment significantly induced production of reactive oxygen species (ROS, which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK, which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  14. The Green Tea Component (-)-Epigallocatechin-3-Gallate Sensitizes Primary Endothelial Cells to Arsenite-Induced Apoptosis by Decreasing c-Jun N-Terminal Kinase-Mediated Catalase Activity.

    Science.gov (United States)

    Kim, Jee-Youn; Choi, Ji-Young; Lee, Hyeon-Ju; Byun, Catherine Jeonghae; Park, Jung-Hyun; Park, Jae Hoon; Cho, Ho-Seong; Cho, Sung-Jin; Jo, Sangmee Ahn; Jo, Inho

    2015-01-01

    The green tea component (-)-epigallocatechin-3-gallate (EGCG) has been shown to sensitize many different types of cancer cells to anticancer drug-induced apoptosis, although it protects against non-cancerous primary cells against toxicity from certain conditions such as exposure to arsenic (As) or ultraviolet irradiation. Here, we found that EGCG promotes As-induced toxicity of primary-cultured bovine aortic endothelial cells (BAEC) at doses in which treatment with each chemical alone had no such effect. Increased cell toxicity was accompanied by an increased condensed chromatin pattern and fragmented nuclei, cleaved poly(ADP-ribose) polymerase (PARP), activity of the pro-apoptotic enzymes caspases 3, 8 and 9, and Bax translocation into mitochondria, suggesting the involvement of an apoptotic signaling pathway. Fluorescence activated cell sorting analysis revealed that compared with EGCG or As alone, combined EGCG and As (EGCG/As) treatment significantly induced production of reactive oxygen species (ROS), which was accompanied by decreased catalase activity and increased lipid peroxidation. Pretreatment with N-acetyl-L-cysteine or catalase reversed EGCG/As-induced caspase activation and EC toxicity. EGCG/As also increased the phosphorylation of c-Jun N-terminal kinase (JNK), which was not reversed by catalase. However, pretreatment with the JNK inhibitor SP600125 reversed all of the observed effects of EGCG/As, suggesting that JNK may be the most upstream protein examined in this study. Finally, we also found that all the observed effects by EGCG/As are true for other types of EC tested. In conclusion, this is firstly to show that EGCG sensitizes non-cancerous EC to As-induced toxicity through ROS-mediated apoptosis, which was attributed at least in part to a JNK-activated decrease in catalase activity.

  15. Bacillus sp. LT3 improves the survival of gnotobiotic brine shrimp (Artemia franciscana) larvae challenged with Vibrio campbellii by enhancing the innate immune response and by decreasing the activity of shrimp-associated vibrios.

    Science.gov (United States)

    Niu, Yufeng; Defoirdt, Tom; Baruah, Kartik; Van de Wiele, Tom; Dong, Shuanglin; Bossier, Peter

    2014-10-10

    Bacteria belonging to the genus Bacillus are amongst the most intensively studied group of bacteria for use as probiotics in aquaculture. However, the exact mechanism of action of these bacteria is often not well described, and the microbiota that are naturally present in cultures of test organisms often compromise the interpretation of the results. The present study aimed to evaluate the putative probiotic effect of Bacillus sp. LT3 in a model system with gnotobiotic brine shrimp Artemia franciscana larvae. The strain significantly increased the survival of brine shrimp larvae challenged with Vibrio campbellii when administered 6h before the challenge. Under these conditions, LT3 was able to colonize the brine shrimp gastrointestinal tract and to decrease the in vivo pathogen activity as indicated by the bioluminescence of the V. campbellii associated with brine shrimp larvae. In order to investigate the effect of the Bacillus strain on the innate immune system of the brine shrimp larvae, prophenoloxidase and transglutaminase mRNA levels were monitored, while heat shock protein 70 mRNA levels were measured as an indicator of physiological stress. Interestingly, 12h after challenge, the prophenoloxidase mRNA level in the larvae pre-treated with LT3 and challenged with V. campbellii was approximately 8-fold higher than in the other treatments. Further, a decreased mRNA level of transglutaminase gene and heat shock protein 70 gene suggested that pretreatment with LT3 results in less stress and tissue damage in the brine shrimp larvae upon V. campbellii challenge. These results indicated that Bacillus sp. LT3 could improve the survival of brine shrimp larvae when challenged with pathogenic V. campbellii, both by decreasing the in vivo activity of the pathogen and by priming the innate immune response through activating the prophenoloxidase system. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Teramura, Takeshi; Takehara, Toshiyuki; Onodera, Yuta; Nakagawa, Koichi; Hamanishi, Chiaki; Fukuda, Kanji

    2012-01-01

    Highlights: ► Mechanical stimulation is an important factor for regulation of stem cell fate. ► Cyclic stretch to human induced pluripotent stem cells activated small GTPase Rho. ► Rho-kinase activation attenuated pluripotency via inhibition of AKT activation. ► This reaction could be reproduced only by transfection of dominant active Rho. ► Rho/ROCK are important molecules in mechanotransduction and control of stemness. -- Abstract: Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.

  17. Oxidation of M252 but not M428 in hu-IgG1 is responsible for decreased binding to and activation of hu-FcγRIIa (His131).

    Science.gov (United States)

    Cymer, Florian; Thomann, Marco; Wegele, Harald; Avenal, Cecile; Schlothauer, Tilman; Gygax, Daniel; Beck, Hermann

    2017-11-01

    Oxidation of monoclonal therapeutic antibodies (mAbs) can affect binding to Fc-receptors and potentially influence pharmacokinetics or effector functions like e.g. antibody dependent cellular phagocytosis (ADCP). Recently, it has been demonstrated that binding to FcγRIIa (H131) is affected by methionine oxidation of the Fc-portion but it is currently unknown which methionine is responsible for decreased binding. We separated an oxidized IgG1 monoclonal antibody based on the oxidation state of methionine 252 and analyzed fractionated material in receptor binding experiments as well as in functional (cell-based) assays. Although the unfractionated mixture demonstrated weaker interaction/activation of the receptor, differently oxidized isolated subspecies can lead both to stronger as well as weaker binding and activation of the histidine variant of FcγRIIa. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. The reproductive performance of female goats treated with melatonin is not improved after introduction to bucks displaying springtime sexual activity if these does are experiencing decreasing body weight/condition score.

    Science.gov (United States)

    Zarazaga, L A; Gatica, M C; Gallego-Calvo, L; Guzmán, J L

    2017-04-01

    The aim of the present work was to determine whether treatment with melatonin modifies the reproductive response of female goats experiencing increasing or decreasing body weight (BW)/body condition score (BCS) when introduced to bucks displaying springtime sexual activity. During natural anoestrus, 53 does were isolated from bucks for a period of 42days and distributed into two groups: 1) low BW/low BCS animals (N=24) (LLg group), which were fed 1.9 times their maintenance requirements so they would experience increasing BW and BCS; and 2) high BW/high BCS animals (N=29) (HHl group), which were fed 0.4 times their maintenance requirements so they would experience decreasing BW and BCS. Half of each group was treated, or not, with melatonin (LLg+Mel N=12, HHl+Mel N=15, LLg-Mel N=12 and HHl-Mel N=14). On 6th May they were introduced to six males, showing natural sexual activity, fitted with marking harnesses (thus permitting the detection of oestrous activity). The ovulation rate was assessed by transrectal ultrasonography and confirmed via the plasma progesterone concentration (measured twice per week in blood samples). Plasma glucose, IGF-1 and non-esterified fatty acid concentrations were also determined, along with the conception rate, fertility, prolificacy and productivity of the does. LH concentrations and LH pulsatility were also recorded in the hours around introduction to the males. 'Oestrous plus ovulation' was observed only in does treated with melatonin. A higher conception rate and greater fertility and productivity were observed among the LLg+Mel does. These females showed higher glucose and IGF-1 concentrations after the introduction of the males. LH concentrations increased after male introduction independent of all other conditions. In conclusion, the present results show that treatment with melatonin does not enhance reproductive performance in does experiencing decreasing BW/BCS, but can improve it when does are experiencing increasing BW

  19. The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity.

    Science.gov (United States)

    Brasil, Girlandia Alexandre; Silva-Cutini, Mirian de Almeida; Moraes, Flávia de Souza Andrade; Pereira, Thiago de Melo Costa; Vasquez, Elisardo Corral; Lenz, Dominik; Bissoli, Nazaré Souza; Endringer, Denise Coutinho; de Lima, Ewelyne Miranda; Biancardi, Vinícia Campana; Maia, June Ferreira; de Andrade, Tadeu Uggere

    We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP 50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP 50 , the lower plateau, and HR range. In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Mechanical stimulation of cyclic tensile strain induces reduction of pluripotent related gene expressions via activation of Rho/ROCK and subsequent decreasing of AKT phosphorylation in human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Teramura, Takeshi, E-mail: teramura@med.kindai.ac.jp [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Takehara, Toshiyuki; Onodera, Yuta [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Nakagawa, Koichi; Hamanishi, Chiaki [Department of Orthopaedic Surgery, Kinki University, Faculty of Medicine, Osaka (Japan); Fukuda, Kanji [Institute of Advanced Clinical Medicine, Kinki University, Faculty of Medicine, Osaka (Japan); Department of Orthopaedic Surgery, Kinki University, Faculty of Medicine, Osaka (Japan)

    2012-01-13

    Highlights: Black-Right-Pointing-Pointer Mechanical stimulation is an important factor for regulation of stem cell fate. Black-Right-Pointing-Pointer Cyclic stretch to human induced pluripotent stem cells activated small GTPase Rho. Black-Right-Pointing-Pointer Rho-kinase activation attenuated pluripotency via inhibition of AKT activation. Black-Right-Pointing-Pointer This reaction could be reproduced only by transfection of dominant active Rho. Black-Right-Pointing-Pointer Rho/ROCK are important molecules in mechanotransduction and control of stemness. -- Abstract: Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.

  1. Adding a purple corn extract in rats supplemented with chia oil decreases gene expression of SREBP-1c and retains Δ5 and Δ6 hepatic desaturase activity, unmodified the hepatic lipid profile.

    Science.gov (United States)

    Reyna Gallegos, Sixto; Torres Arrunátegui, Génesis; Valenzuela, Rodrigo; Rincón-Cervera, Miguel Ángel; Villanueva Espinoza, María Elena

    2018-05-01

    Flavonoids upregulate gene expression of PPAR-α and underregulate the gene expression of SREBP-1c, and their intake increases the plasmatic concentration of n-3 LC-PUFAs. However, the biological mechanisms underlying these effects have not been elucidated. In this work, the effect of oral supplementation of ALA from chia (Salvia hispanica L.) seed oil and anthocyanins from a purple corn extract (PCE) on gene expression of SREBP-1c, PPAR-α and Δ5 and Δ6 desaturases (Δ5D and Δ6D), the activity of these enzymes in the liver as well as the hepatic lipid profile were evaluated in thirty-six female Sprague Dawley rats whose diet was supplemented with olive oil (OL), chia oil (CH), olive oil and PCE (OL + PCE) or chia oil and PCE (CH + PCE). Gene expression of PPAR-α was significantly higher when supplemented with CH and CH + PCE, SREBP-1c gene expression was higher when supplemented with chia oil. CH supplementation enhanced Δ5D expression whereas no significant differences between treatments were observed concerning Δ6D gene expression. Activities of both desaturases were increased by including olive oil (OL + PCE and OL), and they were found to be higher in CH + PCE respect to CH for both enzymes. The ALA and n-3 LCPUFAs hepatic content was higher with CH, decreasing the levels of AA and n-6 LCPUFAs. It is concluded that the joint action of flavonoids such as anthocyanins and ALA show an anti-adipogenic effect. Desaturase activity was inhibited by ALA and kept by the anthocyanins from PCE, thus anthocyanins would exert a protective effect on the desaturase activity but they would not affect on its gene expression, however, high doses of ALA increased the production of its metabolites, masking the effect of PCE. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Decreased levels of active uPA and KLK8 assessed by [111 In]MICA-401 binding correlate with the seizure burden in an animal model of temporal lobe epilepsy.

    Science.gov (United States)

    Missault, Stephan; Peeters, Lore; Amhaoul, Halima; Thomae, David; Van Eetveldt, Annemie; Favier, Barbara; Thakur, Anagha; Van Soom, Jeroen; Pitkänen, Asla; Augustyns, Koen; Joossens, Jurgen; Staelens, Steven; Dedeurwaerdere, Stefanie

    2017-09-01

    Urokinase-type plasminogen activator (uPA) and kallikrein-related peptidase 8 (KLK8) are serine proteases that contribute to extracellular matrix (ECM) remodeling after brain injury. They can be labelled with the novel radiotracer [ 111 In]MICA-401. As the first step in exploring the applicability of [ 111 In]MICA-401 in tracing the mechanisms of postinjury ECM reorganization in vivo, we performed in vitro and ex vivo studies, assessing [ 111 In]MICA-401 distribution in the brain in two animal models: kainic acid-induced status epilepticus (KASE) and controlled cortical impact (CCI)-induced traumatic brain injury (TBI). In the KASE model, in vitro autoradiography with [ 111 In]MICA-401 was performed at 7 days and 12 weeks post-SE. To assess seizure burden, rats were monitored using video-electroencephalography (EEG) for 1 month before the 12-week time point. In the CCI model, in vitro autoradiography was performed at 4 days and ex vivo autoradiography at 7 days post-TBI. At 7 days post-SE, in vitro autoradiography revealed significantly decreased [ 111 In]MICA-401 binding in hippocampal CA3 subfield and extrahippocampal temporal lobe (ETL). In the chronic phase, when animals had developed spontaneous seizures, specific binding was decreased in CA3 and CA1/CA2 subfields of hippocampus, dentate gyrus, ETL, and parietal cortex. Of interest, KASE rats with the highest frequency of seizures had the lowest hippocampal [ 111 In]MICA-401 binding (r = -0.76, p ≤ 0.05). Similarly, at 4 days post-TBI, in vitro [ 111 In]MICA-401 binding was significantly decreased in medial and lateral perilesional cortex and ipsilateral dentate gyrus. Ex vivo autoradiography at 7 days post-TBI, however, revealed increased tracer uptake in perilesional cortex and hippocampus, which was likely related to tracer leakage due to blood-brain barrier (BBB) disruption. Strong association of reduced [ 111 In]MICA-401 binding with seizure burden in the KASE model suggests that analysis of reduced

  3. Topical corticosteroids do not revert the activated phenotype of eosinophils in eosinophilic esophagitis but decrease surface levels of CD18 resulting in diminished adherence to ICAM-1, ICAM-2, and endothelial cells.

    Science.gov (United States)

    Lingblom, Christine; Bergquist, Henrik; Johnsson, Marianne; Sundström, Patrik; Quiding-Järbrink, Marianne; Bove, Mogens; Wennerås, Christine

    2014-12-01

    Swallowed topical corticosteroids are the standard therapy for eosinophilic esophagitis (EoE) in adults. Eosinophils in the blood of untreated EoE patients have an activated phenotype. Our aim was to determine if corticosteroids restore the phenotype of eosinophils to a healthy phenotype and if certain cell-surface molecules on blood eosinophils correlate with eosinophilic infiltration of the esophagus. Levels of eight surface markers on eosinophils from treated and untreated EoE patients were determined by flow cytometry and analyzed using multivariate methods of pattern recognition. Corticosteroid-treated EoE patients' eosinophils had decreased levels of CD18 compared to both untreated patients and healthy controls, but maintained their activated phenotype. CD18 expression correlated positively with eosinophil numbers in the esophagus and promoted the adherence of eosinophils to ICAM-1, ICAM-2, and to endothelial cells. The diminished expression of CD18 may be one mechanism behind the reduced entry of eosinophils into the esophagus in corticosteroid-treated EoE patients.

  4. Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486.

    Science.gov (United States)

    Kalandadze, Avtandil; Wu, Ying; Robinson, Michael B

    2002-11-29

    Na(+)-dependent glutamate transporters are required for the clearance of extracellular glutamate and influence both physiological and pathological effects of this excitatory amino acid. In the present study, the effects of a protein kinase C (PKC) activator on the cell surface expression and activity of the GLT-1 subtype of glutamate transporter were examined in two model systems, primary co-cultures of neurons and astrocytes that endogenously express GLT-1 and C6 glioma cells transfected with GLT-1. In both systems, activation of PKC with phorbol ester caused a decrease in GLT-1 cell surface expression. This effect is opposite to the one observed for the EAAC1 subtype of glutamate transporter (Davis, K. E., Straff, D. J., Weinstein, E. A., Bannerman, P. G., Correale, D. M., Rothstein, J. D., and Robinson, M. B. (1998) J. Neurosci. 18, 2475-2485). Several recombinant chimeric proteins between GLT-1 and EAAC1 transporter subtypes were generated to identify domains required for the subtype-specific redistribution of GLT-1. We identified a carboxyl-terminal domain consisting of 43 amino acids (amino acids 475-517) that is required for PKC-induced GLT-1 redistribution. Mutation of a non-conserved serine residue at position 486 partially attenuated but did not completely abolish the PKC-dependent redistribution of GLT-1. Although we observed a phorbol ester-dependent incorporation of (32)P into immunoprecipitable GLT-1, mutation of serine 486 did not reduce this signal. We also found that chimeras containing the first 446 amino acids of GLT-1 were not functional unless amino acids 475-517 of GLT-1 were also present. These non-functional transporters were not as efficiently expressed on the cell surface and migrated to a smaller molecular weight, suggesting that a subtype-specific interaction is required for the formation of functional transporters. These studies demonstrate a novel effect of PKC on GLT-1 activity and define a unique carboxyl-terminal domain as an

  5. ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity

    Directory of Open Access Journals (Sweden)

    Bu Guojun

    2007-07-01

    Full Text Available Abstract Background The generation of the amyloid-β peptide (Aβ through the proteolytic processing of the amyloid precursor protein (APP is a central event in the pathogenesis of Alzheimer's disease (AD. Recent studies highlight APP endocytosis and localization to lipid rafts as important events favoring amyloidogenic processing. However, the precise mechanisms underlying these events are poorly understood. ApoER2 is a member of the low density lipoprotein receptor (LDL-R family exhibiting slow endocytosis rate and a significant association with lipid rafts. Despite the important neurophysiological roles described for ApoER2, little is known regarding how ApoER2 regulates APP trafficking and processing. Results Here, we demonstrate that ApoER2 physically interacts and co-localizes with APP. Remarkably, we found that ApoER2 increases cell surface APP levels and APP association with lipid rafts. The increase of cell surface APP requires the presence of ApoER2 cytoplasmic domain and is a result of decreased APP internalization rate. Unexpectedly, ApoER2 expression correlated with a significant increase in Aβ production and reduced levels of APP-CTFs. The increased Aβ production was dependent on the integrity of the NPxY endocytosis motif of ApoER2. We also found that expression of ApoER2 increased APP association with lipid rafts and increased γ-secretase activity, both of which might contribute to increased Aβ production. Conclusion These findings show that ApoER2 negatively affects APP internalization. However, ApoER2 expression stimulates Aβ production by shifting the proportion of APP from the non-rafts to the raft membrane domains, thereby promoting β-secretase and γ-secretase mediated amyloidogenic processing and also by incrementing the activity of γ-secretase.

  6. Application Anti Microbial Activity Test and Direct Inoculation of Urinary Specimen Test to Increase the Quality of Results and Decrease the Production Cost in Clinical Microbiology Laboratory, Sanglah General Hospital Hospital, Bali-Indonesia

    Directory of Open Access Journals (Sweden)

    Nyoman Sri-Budayanti

    2012-05-01

    Full Text Available Objective: Urinary tract infection (UTI is the most common bacterial infection in general practice and in hospitals. Fast and accurate urine culture and sensitivity test are needed for adequate therapy. Anti Microbial Activity test (AMA test that is used to detect the presence of antibiotics in urine specimens is not commonly used in clinical microbiology laboratories. Some laboratories are still using indirect inoculation technique using enriched media before inoculating onto the agar media. The aim of this research is to compare results of urinary examination of direct inoculation technique with AMA test with indirect inoculation technique without AMA test.Methods: A number of 210 urine specimens were collected in Clinical Microbiology Laboratory at Sanglah General Hospital within a time period between 16 June until 16 July 2009.Results: Antibiotics were detected in 40% of the urinary specimens; whereas 48.1% showed no evidence of UTI, that is negative AMA test and sterile urinary culture or colony growth < 105 CFU/ml. Only 11.9% of the specimens indicates urinary tract infections. The examination can be completed within 2-3 days which is shorter than indirect inoculation test which require 5-7 days. Direct inoculation technique can reduce the cost of production three-fold the costs require for an indirect inoculation test.Conclusions: Application of AMA test and direct inoculation technique can give results more rapidly, reliable and useful for clinicians. This also decrease the laboratory’s cost of production.

  7. Airplane radiation dose decrease during a strong Forbush decrease

    Czech Academy of Sciences Publication Activity Database

    Spurný, František; Kudela, K.; Dachev, T.

    2004-01-01

    Roč. 2, S05001 (2004), s. 1-4 ISSN 1542-7390 Grant - others:EC project(XE) FIGM-CT2000-00068 Institutional research plan: CEZ:AV0Z1048901 Keywords : airplane dose * Forbush decrease * cosmic rays Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders

  8. Magical thinking decreases across adulthood.

    Science.gov (United States)

    Brashier, Nadia M; Multhaup, Kristi S

    2017-12-01

    Magical thinking, or illogical causal reasoning such as superstitions, decreases across childhood, but almost no data speak to whether this developmental trajectory continues across the life span. In four experiments, magical thinking decreased across adulthood. This pattern replicated across two judgment domains and could not be explained by age-related differences in tolerance of ambiguity, domain-specific knowledge, or search for meaning. These data complement and extend findings that experience, accumulated over decades, guides older adults' judgments so that they match, or even exceed, young adults' performance. They also counter participants' expectations, and cultural sayings (e.g., "old wives' tales"), that suggest that older adults are especially superstitious. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  9. Does fertility decrease household consumption?

    OpenAIRE

    Jungho Kim; Henriette Engelhardt; Alexia Fürnkranz-Prskawetz; Arnstein Aassve

    2009-01-01

    This paper presents an empirical analysis of the relationship between fertility and a direct measure of poverty for Indonesia, a country, which has experienced unprecedented economic growth and sharp fertility declines over recent decades. It focuses on illustrating the sensitivity of the effect of fertility on household consumption with respect to the equivalence scale by applying the propensity score matching method. The analysis suggests that a newborn child decreases household consumption...

  10. Distraction decreases prefrontal oxygenation: A NIRS study.

    Science.gov (United States)

    Ozawa, Sachiyo; Hiraki, Kazuo

    2017-04-01

    When near-infrared spectroscopy (NIRS) is used to measure emotion-related cerebral blood flow (CBF) changes in the prefrontal cortex regions, the functional distinction of CBF changes is often difficult because NIRS is unable to measure neural activity in deeper brain regions that play major roles in emotional processing. The CBF changes could represent cognitive control of emotion and emotional responses to emotional materials. Supposing that emotion-related CBF changes in the prefrontal cortex regions during distraction are emotional responses, we examined whether oxygenated hemoglobin (oxyHb) decreases. Attention-demanding tasks cause blood flow decreases, and we thus compared the effects of visually paced tapping with different tempos, on distraction. The results showed that the oxyHb level induced by emotional stimulation decreased with fast-tempo tapping significantly more than slow-tempo tapping in ventral medial prefrontal cortex regions. Moreover, a Global-Local task following tapping showed significantly greater local-minus-global response time (RT) difference scores in the fast- and mid-tempo condition compared with those in the slow-tempo, suggesting an increased attentional focus, and decreased negative emotion. The overall findings indicate that oxyHb changes in a relatively long distraction task, as measured by NIRS, are associated with emotional responses, and oxyHb can be decreased by successfully performing attention-demanding distraction tasks. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A single, specific thymine mutation in the ComK-Binding site severely decreases binding and transcription activation by the competence transcription factor ComK of Bacillus subtilis

    NARCIS (Netherlands)

    Susanna, Kim A.; Mironczuk, Aleksandra M.; Smits, Wiep Klaas; Hamoen, Leendert W.; Kuipers, Oscar P.

    The competence transcription factor ComK plays a central role in competence development in Bacillus subtilis by activating the transcription of the K regulon. ComK-activated genes are characterized by the presence of a specific sequence to which ComK binds, a K-box, in their upstream DNA region.

  12. Decreasing Fires in Mediterranean Europe.

    Directory of Open Access Journals (Sweden)

    Marco Turco

    Full Text Available Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value. These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011 and a mixed trend in Portugal (1980-2011. Similar overall results were found for the annual number of fires (NF, which globally decreased by about 12600 in the study period (about -59%, except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  13. Decreasing Fires in Mediterranean Europe.

    Science.gov (United States)

    Turco, Marco; Bedia, Joaquín; Di Liberto, Fabrizio; Fiorucci, Paolo; von Hardenberg, Jost; Koutsias, Nikos; Llasat, Maria-Carmen; Xystrakis, Fotios; Provenzale, Antonello

    2016-01-01

    Forest fires are a serious environmental hazard in southern Europe. Quantitative assessment of recent trends in fire statistics is important for assessing the possible shifts induced by climate and other environmental/socioeconomic changes in this area. Here we analyse recent fire trends in Portugal, Spain, southern France, Italy and Greece, building on a homogenized fire database integrating official fire statistics provided by several national/EU agencies. During the period 1985-2011, the total annual burned area (BA) displayed a general decreasing trend, with the exception of Portugal, where a heterogeneous signal was found. Considering all countries globally, we found that BA decreased by about 3020 km2 over the 27-year-long study period (i.e. about -66% of the mean historical value). These results are consistent with those obtained on longer time scales when data were available, also yielding predominantly negative trends in Spain and France (1974-2011) and a mixed trend in Portugal (1980-2011). Similar overall results were found for the annual number of fires (NF), which globally decreased by about 12600 in the study period (about -59%), except for Spain where, excluding the provinces along the Mediterranean coast, an upward trend was found for the longer period. We argue that the negative trends can be explained, at least in part, by an increased effort in fire management and prevention after the big fires of the 1980's, while positive trends may be related to recent socioeconomic transformations leading to more hazardous landscape configurations, as well as to the observed warming of recent decades. We stress the importance of fire data homogenization prior to analysis, in order to alleviate spurious effects associated with non-stationarities in the data due to temporal variations in fire detection efforts.

  14. Technologies for Decreasing Mining Losses

    Science.gov (United States)

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin

    2013-12-01

    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  15. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-time bacteremia in Funen County, Denmark, during 2000-2008 (N = 7786). We reported mean and annual incidence rates (per 100,000 person-years), overall and by place of acquisition. Trends were estimated using a Poisson regression model. RESULTS: The overall incidence rate was 215.7, including 99.0 for community......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p incidence rate of community-acquired bacteremia decreased by 25.6% from 119.0 to 93.8 (3.7% annually, p

  16. Price of forest chips decreasing

    International Nuclear Information System (INIS)

    Hakkila, P.

    2001-01-01

    Use of forest chips was studied in 1999 in the national Puuenergia (Wood Energy) research program. Wood combusting heating plants were questioned about are the main reasons restricting the increment of the use of forest chips. Heating plants, which did not use forest chips at all or which used less than 250 m 3 (625 bulk- m 3 ) in 1999 were excluded. The main restrictions for additional use of forest chips were: too high price of forest chips; lack of suppliers and/or uncertainty of deliveries; technical problems of reception and processing of forest chips; insufficiency of boiler output especially in winter; and unsatisfactory quality of chips. The price of forest chips becomes relatively high because wood biomass used for production of forest chips has to be collected from wide area. Heavy equipment has to be used even though small fragments of wood are processed, which increases the price of chips. It is essential for forest chips that the costs can be pressed down because competition with fossil fuels, peat and industrial wood residues is hard. Low market price leads to the situation in which forest owner gets no price of the raw material, the entrepreneurs operate at the limit of profitability and renovation of machinery is difficult, and forest chips suppliers have to sell the chips at prime costs. Price of forest chips has decreased significantly during the past decade. Nominal price of forest chips is now lower than two decades ago. The real price of chips has decreased even more than the nominal price, 35% during the past decade and 20% during the last five years. Chips, made of small diameter wood, are expensive because the price includes the felling costs and harvesting is carried out at thinning lots. Price is especially high if chips are made of delimbed small diameter wood due to increased the work and reduced amount of chips. The price of logging residue chips is most profitable because cutting does not cause additional costs. Recovery of chips is

  17. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    Science.gov (United States)

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  18. Rigidity spectrum of Forbush decrease

    International Nuclear Information System (INIS)

    Sakakibara, S.; Munakata, K.; Nagashima, K.

    1985-01-01

    Using data from neutron monitors and muon telescopes at surface and underground stations, the average rigidity spectrum of Forbush decreases (Fds) during the period of 1978-1982 were obtained. Thirty eight Ed-events are classified into two groups, Hard Fd and Soft FD according to size of Fd at the Sakashita station. It is found that a spectral form of a fractional-power type (P to the-gamma sub 1 (P+P sub c) to the -gamma sub2) is more suitable than that of a power-exponential type or of a power type with an upper limiting rigidity. The best fitted spectrum of the fractional-power type is expressed by gamma sub1 = 0.37, gamma sub2 = 0.89 and P subc = 10 GV for Hard Fd and gamma sub1 = 0.77, gamma sub2 = 1.02 and P sub c - 14GV for Soft Fd

  19. Method of decreasing nuclear power

    International Nuclear Information System (INIS)

    Masuda, Hiromi

    1987-01-01

    Purpose: To easily attain the power decreasing in a HWLWR type reactor and improve the reactor safety. Method: The method is applied to a nuclear reactor in which the reactor reactivity is controlled by control rods and liquid posions dissolved in moderators. Means for forecasting the control rod operation amount required for the reactor power down and means for removing liquid poisons in the moderators are provided. The control rod operation amount required for the power down is forecast before the power down and the liquid poisons in the moderators are removed. Then, the control rods are inserted into a deep insertion position to reduce the reactor power. This invention can facilitate easy power down, as well as provide effects of improving the controllability in the usual operation and of avoiding abrupt power down which leads to an improved availability. (Kamimura, M.)

  20. Metformin affects macrophages' phenotype and improves the activity of glutathione peroxidase, superoxide dismutase, catalase and decreases malondialdehyde concentration in a partially AMPK-independent manner in LPS-stimulated human monocytes/macrophages.

    Science.gov (United States)

    Bułdak, Łukasz; Łabuzek, Krzysztof; Bułdak, Rafał Jakub; Kozłowski, Michał; Machnik, Grzegorz; Liber, Sebastian; Suchy, Dariusz; Duława-Bułdak, Anna; Okopień, Bogusław

    2014-06-01

    Diabetic patients experience accelerated atherosclerosis. Metformin is a cornerstone of the current therapy of type 2 diabetes. Macrophages are the key cells associated with the development of atherosclerotic plaques. Therefore, our aim was to assess the in vitro effects of metformin on macrophages and its influence on the mechanisms involved in the development of atherosclerosis. Peripheral blood mononuclear cells were obtained from the group including 16 age-matched healthy non-smoking volunteers aged 18-40 years. Monocytes were further incubated with metformin, LPS and compound C--a pharmacological inhibitor of AMPK. The impact of metformin on oxidative stress markers, antioxidative properties, inflammatory cytokines and phenotypical markers of macrophages was studied. We showed that macrophages treated with metformin expressed less reactive oxygen species (ROS), which resulted from increased antioxidative potential. Furthermore, a reduction in inflammatory cytokines was observed. We also observed a phenotypic shift toward the alternative activation of macrophages that was induced by metformin. All the aforementioned results resulted from AMPK activation, but a residual activity of metformin after AMPK blockade was still noticeable even after inhibition of AMPK by compound C. Authors believe that metformin-based therapy, a cornerstone in diabetes therapy, not only improves the prognosis of diabetics by reducing blood glucose but also by reducing oxidative stress, inflammatory cytokine production and the shift toward alternative activation of macrophages. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly.

    Science.gov (United States)

    Rondanelli, Mariangela; Klersy, Catherine; Terracol, Gilles; Talluri, Jacopo; Maugeri, Roberto; Guido, Davide; Faliva, Milena A; Solerte, Bruno S; Fioravanti, Marisa; Lukaski, Henry; Perna, Simone

    2016-03-01

    Interventions to attenuate the adverse effects of age-related loss of skeletal muscle and function include increased physical activity and nutritional supplementation. This study tested the hypothesis that nutritional supplementation with whey protein (22 g), essential amino acids (10.9 g, including 4 g leucine), and vitamin D [2.5 μg (100 IU)] concurrent with regular, controlled physical activity would increase fat-free mass, strength, physical function, and quality of life, and reduce the risk of malnutrition in sarcopenic elderly persons. A total of 130 sarcopenic elderly people (53 men and 77 women; mean age: 80.3 y) participated in a 12-wk randomized, double-blind, placebo-controlled supplementation trial. All participants concurrently took part in a controlled physical activity program. We examined body composition with dual-energy X-ray absorptiometry, muscle strength with a handgrip dynamometer, and blood biochemical indexes of nutritional and health status, and evaluated global nutritional status, physical function, and quality of life before and after the 12 wk of intervention. Compared with physical activity and placebo, supplementation plus physical activity increased fat-free mass (1.7-kg gain, P nutritional assessment (P = 0.003), and insulin-like growth factor I (P = 0.002), and lowered C-reactive protein (P = 0.038). Supplementation with whey protein, essential amino acids, and vitamin D, in conjunction with age-appropriate exercise, not only boosts fat-free mass and strength but also enhances other aspects that contribute to well-being in sarcopenic elderly. This trial was registered at clinicaltrials.gov as NCT02402608. © 2016 American Society for Nutrition.

  2. Decreasing vortex flux in channels

    International Nuclear Information System (INIS)

    Migaj, V.K.; Nosova, I.S.

    1979-01-01

    A new method for reducing vortex flow losses in power plant channels is suggested. The method is based on vortex splitting in vortex flow areas with transverse barriers placed on the channel walls. The upper barrier ends are at the level of the upper boundary of the vortex area and don't protrude to the active flow beyond this boundary. The effectiveness of the method suggested is illustrated taking as an example the investigation of square and flat channels with abrupt widening in one plane, diffusers with widening in one plane, or a rectangualr bend. It is shown that splitting the vortex areas with transverse barriers in the channels results in reduction of hydraulic losses by 10-25%. The above method is characteristic of an extreme simplicity, its application doesn't require changes in the channel shape nor installation of any devices in the flow

  3. α-Asarone Attenuates Cognitive Deficit in a Pilocarpine-Induced Status Epilepticus Rat Model via a Decrease in the Nuclear Factor-κB Activation and Reduction in Microglia Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hui-juan Liu

    2017-12-01

    Full Text Available BackgroundTemporal lobe epilepsy (TLE is one of the most drug-resistant types of epilepsy with about 80% of TLE patients falling into this category. Increasing evidence suggests that neuroinflammation, which has a critical role in the epileptogenesis of TLE, is associated with microglial activation. Therefore, agents that act toward the alleviation in microglial activation and the attenuation of neuroinflammation are promising candidates to treat TLE. α-Asarone is a major active ingredient of the Acori Graminei Rhizoma used in Traditional Chinese Medicine, which has been used to improve various disease conditions including stroke and convulsions. In addition, an increasing number of studies suggested that α-asarone can attenuate microglia-mediated neuroinflammation. Thus, we hypothesized that α-asarone is a promising neuroprotective agent for the treatment of the TLE.MethodsThe present study evaluated the therapeutic effects of α-asarone on microglia-mediated neuroinflammation and neuroprotection in vitro and in vivo, using an untreated control group, a status epilepticus (SE-induced group, and an SE-induced α-asarone pretreated group. A pilocarpine-induced rat model of TLE was established to investigate the neuroprotective effects of α-asarone in vivo. For the in vitro study, lipopolysaccharide (LPS-stimulated primary cultured microglial cells were used.ResultsThe results indicated that the brain microglial activation in the rats of the SE rat model led to important learning and memory deficit. Preventive treatment with α-asarone restrained microglial activation and reduced learning and memory deficit. In the in vitro studies, α-asarone significantly suppressed proinflammatory cytokine production in primary cultured microglial cells and attenuated the LPS-stimulated neuroinflammatory responses. Our mechanistic study revealed that α-asarone inhibited inflammatory processes by regulation the transcription levels of kappa-B, by blocking

  4. A Naturally Occurring Mutation K220T in the Pleiotropic Activator PrfA of Listeria Monocytogenes Results in a Loss of Virulence Due to Decreasing DNA-Binding Affinity

    Energy Technology Data Exchange (ETDEWEB)

    Velge,P.; Herler, M.; Johansson, J.; Roches, S.; Temoin, S.; Fedorov, A.; Gracieux, P.; Almo, S.; Goebel, W.; Cossart, P.

    2007-01-01

    The sequencing of prfA, encoding the transcriptional regulator of virulence genes, in 26 low-virulence field Listeria monocytogenes strains showed that eight strains exhibited the same single amino-acid substitution: PrfAK220T. These strains exhibited no expression of PrfA-regulated proteins and thus no virulence. This substitution inactivated PrfA, since expression of the PrfAK220T mutant gene in an EGD{Delta}prfA strain did not restore the haemolytic and phosphatidylcholine phospholipase C activities, in contrast to the wild-type prfA gene. The substitution of the lysine at position 220 occurred in the helix H. However, the data showed that the PrfAK220T protein is dimerized just as well as its wild-type counterpart, but does not bind to PrfA-boxes. PrfAK220T did not form a PrfA-DNA complex in electrophoretic mobility shift assays, but low concentrations of CI complexes (PrfAK220T-RNA polymerase-DNA complex) were formed by adding RNA polymerase, suggesting that PrfA interacted with RNA polymerase in solution in the absence of DNA. Formation of some transcriptionally active complexes was confirmed by in vitro runoff transcription assays and quantitative RT-PCR. Crystallographic analyses described the structure of native PrfA and highlighted the key role of allosteric changes in the activity of PrfA and especially the role of the Lys220 in the conformation of the helix-turn-helix (HTH) motif.

  5. Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Baumann, Sven [Department of Metabolomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Schorsch, Katrin [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Trump, Saskia; Lehmann, Irina [Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Bergen, Martin von [Department of Proteomics, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Environmental Immunology, Helmholtz-Centre for Environmental Research — UFZ, Permoserstr. 15, 04318 Leipzig (Germany); Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg (Denmark); Tomm, Janina M., E-mail: Janina.tomm@ufz.de [Department of Proteomics, Helmholtz-Centre for Environmental Resear